Conference Coverage

For surgical patients on chronic opioid therapy, the goals of pain management are to provide adequate analgesia, prevent withdrawal, and avoid relapse or worsening of opioid use, according to Stephanie B. Jones, MD, professor and chair of anesthesiology at Albany Medical College, New York.

“[With] any patient coming in for any sort of surgery, you should be considering multimodal pain management. That applies to the opioid use disorder patient as well,” Dr. Jones said in a presentation at the virtual Annual Minimally Invasive Surgery Symposium sponsored by Global Academy for Medical Education.

“The challenge of opioid-tolerant patients or opioid abuse patients is twofold – tolerance and hyperalgesia,” Dr. Jones said. Patient tolerance changes how patients perceive pain and respond to medication. Clinicians need to consider the “opioid debt,” defined as the daily amount of opioid medication required by opioid-dependent patients to maintain their usual prehospitalization opioid levels, she explained. Also consider hyperalgesia, a change in pain perception “resulting in an increase in pain sensitivity to painful stimuli, thereby decreasing the analgesic effects of opioids,” Dr. Jones added.

A multimodal approach to pain management in patients on chronic opioids can include some opioids as appropriate, Dr. Jones said. Modulation of pain may draw on epidurals and nerve blocks, as well as managing CNS perception of pain through opioids or acetaminophen, and also using systemic options such as alpha-2 agonists and tramadol, she said.

Studies have shown that opioid abuse or dependence were associated with increased readmission rates, length of stay, and health care costs in surgery patients, said Dr. Jones. However, switching opioids and managing equivalents is complex, and “equianalgesic conversions serve only as a general guide to estimate opioid dose equivalents,” according to UpToDate’s, “Management of acute pain in the patient chronically using opioids,” she said.

Dr. Jones also addressed the issue of using hospitalization as an opportunity to help patients with untreated opioid use disorder. Medication-assisted options include methadone, buprenorphine, and naltrexone.

“One problem with methadone is that there are a lot of medications interactions,” she said. Buprenorphine has the advantage of being long-lasting, and is formulated with naloxone which deters injection. “Because it is a partial agonist, there is a lower risk of overdose and sedation,” and it has fewer medication interactions. However, some doctors are reluctant to prescribe it and there is some risk of medication diversion, she said.

Naltrexone is newer to the role of treating opioid use disorder, Dr. Jones said. “It can cause acute withdrawal because it is a full opioid antagonist,” she noted. However, naltrexone itself causes no withdrawal if stopped, and no respiratory depression or sedation, said Dr. Jones.

“Utilize addiction services in your hospital if you suspect a patient may be at risk for opioid use disorder,” and engage these services early, she emphasized.

Global Academy for Medical Education and this news organization are owned by the same parent company.

Dr. Jones had no financial conflicts to disclose.

For surgical patients on chronic opioid therapy, the goals of pain management are to provide adequate analgesia, prevent withdrawal, and avoid relapse or worsening of opioid use, according to Stephanie B. Jones, MD, professor and chair of anesthesiology at Albany Medical College, New York.

“[With] any patient coming in for any sort of surgery, you should be considering multimodal pain management. That applies to the opioid use disorder patient as well,” Dr. Jones said in a presentation at the virtual Annual Minimally Invasive Surgery Symposium sponsored by Global Academy for Medical Education.

“The challenge of opioid-tolerant patients or opioid abuse patients is twofold – tolerance and hyperalgesia,” Dr. Jones said. Patient tolerance changes how patients perceive pain and respond to medication. Clinicians need to consider the “opioid debt,” defined as the daily amount of opioid medication required by opioid-dependent patients to maintain their usual prehospitalization opioid levels, she explained. Also consider hyperalgesia, a change in pain perception “resulting in an increase in pain sensitivity to painful stimuli, thereby decreasing the analgesic effects of opioids,” Dr. Jones added.

A multimodal approach to pain management in patients on chronic opioids can include some opioids as appropriate, Dr. Jones said. Modulation of pain may draw on epidurals and nerve blocks, as well as managing CNS perception of pain through opioids or acetaminophen, and also using systemic options such as alpha-2 agonists and tramadol, she said.

Studies have shown that opioid abuse or dependence were associated with increased readmission rates, length of stay, and health care costs in surgery patients, said Dr. Jones. However, switching opioids and managing equivalents is complex, and “equianalgesic conversions serve only as a general guide to estimate opioid dose equivalents,” according to UpToDate’s, “Management of acute pain in the patient chronically using opioids,” she said.

Dr. Jones also addressed the issue of using hospitalization as an opportunity to help patients with untreated opioid use disorder. Medication-assisted options include methadone, buprenorphine, and naltrexone.

“One problem with methadone is that there are a lot of medications interactions,” she said. Buprenorphine has the advantage of being long-lasting, and is formulated with naloxone which deters injection. “Because it is a partial agonist, there is a lower risk of overdose and sedation,” and it has fewer medication interactions. However, some doctors are reluctant to prescribe it and there is some risk of medication diversion, she said.

Naltrexone is newer to the role of treating opioid use disorder, Dr. Jones said. “It can cause acute withdrawal because it is a full opioid antagonist,” she noted. However, naltrexone itself causes no withdrawal if stopped, and no respiratory depression or sedation, said Dr. Jones.

“Utilize addiction services in your hospital if you suspect a patient may be at risk for opioid use disorder,” and engage these services early, she emphasized.

Global Academy for Medical Education and this news organization are owned by the same parent company.

Dr. Jones had no financial conflicts to disclose.

For surgical patients on chronic opioid therapy, the goals of pain management are to provide adequate analgesia, prevent withdrawal, and avoid relapse or worsening of opioid use, according to Stephanie B. Jones, MD, professor and chair of anesthesiology at Albany Medical College, New York.

“[With] any patient coming in for any sort of surgery, you should be considering multimodal pain management. That applies to the opioid use disorder patient as well,” Dr. Jones said in a presentation at the virtual Annual Minimally Invasive Surgery Symposium sponsored by Global Academy for Medical Education.

“The challenge of opioid-tolerant patients or opioid abuse patients is twofold – tolerance and hyperalgesia,” Dr. Jones said. Patient tolerance changes how patients perceive pain and respond to medication. Clinicians need to consider the “opioid debt,” defined as the daily amount of opioid medication required by opioid-dependent patients to maintain their usual prehospitalization opioid levels, she explained. Also consider hyperalgesia, a change in pain perception “resulting in an increase in pain sensitivity to painful stimuli, thereby decreasing the analgesic effects of opioids,” Dr. Jones added.

A multimodal approach to pain management in patients on chronic opioids can include some opioids as appropriate, Dr. Jones said. Modulation of pain may draw on epidurals and nerve blocks, as well as managing CNS perception of pain through opioids or acetaminophen, and also using systemic options such as alpha-2 agonists and tramadol, she said.

Studies have shown that opioid abuse or dependence were associated with increased readmission rates, length of stay, and health care costs in surgery patients, said Dr. Jones. However, switching opioids and managing equivalents is complex, and “equianalgesic conversions serve only as a general guide to estimate opioid dose equivalents,” according to UpToDate’s, “Management of acute pain in the patient chronically using opioids,” she said.

Dr. Jones also addressed the issue of using hospitalization as an opportunity to help patients with untreated opioid use disorder. Medication-assisted options include methadone, buprenorphine, and naltrexone.

“One problem with methadone is that there are a lot of medications interactions,” she said. Buprenorphine has the advantage of being long-lasting, and is formulated with naloxone which deters injection. “Because it is a partial agonist, there is a lower risk of overdose and sedation,” and it has fewer medication interactions. However, some doctors are reluctant to prescribe it and there is some risk of medication diversion, she said.

Naltrexone is newer to the role of treating opioid use disorder, Dr. Jones said. “It can cause acute withdrawal because it is a full opioid antagonist,” she noted. However, naltrexone itself causes no withdrawal if stopped, and no respiratory depression or sedation, said Dr. Jones.

“Utilize addiction services in your hospital if you suspect a patient may be at risk for opioid use disorder,” and engage these services early, she emphasized.

Global Academy for Medical Education and this news organization are owned by the same parent company.

Dr. Jones had no financial conflicts to disclose.

A novel program that aims to automate the Sharp-van der Heijde scoring of radiographs of patients with rheumatoid arthritis has shown good reliability in identifying regions of interest and matching human reader scoring for joint-space narrowing, according to a report given at the annual European Congress of Rheumatology, held online this year because of COVID-19.

Courtesy Dr. Thomas Deimel

First author and presenter Thomas Deimel, MD, and colleagues at the Medical University of Vienna said their program, called autoscoRA, may be a solution to the problem of readers having to make subjective calls on the severity of damage seen on radiographs.

Although the work continues to be validated, Dr. Deimel, a resident at the university, is confident in the system as is. “I think for joint space narrowing, we’re there at the point where this could be used and could be as good as a human reader in terms of reliability,” he said in an interview. To find out, the group plans to compare the variability between autoscoRA and a gold-standard human reader against the variability seen between human readers. If the two measures of variability are similar, it would provide a strong endorsement.

The effort is far from the first to develop an automatic scoring system for RA images, but no fully automated system has emerged as reliable, according to Dr. Deimel. He thinks one main issue for others has been lack of access to a sufficient data set to train systems. It can be difficult to find enough training images because many types of joint damage are comparatively uncommon. The problem is made even worse because images can be hard to interpret: The shapes that the system must decipher can be misleading, especially in positions of tendon insertion or ligament attachment that can resemble damage. Differing angles of view between various training images can also complicate matters.

The autoscoRA program is based on modifications of a form of convolutional neural network called the VGG16 architecture. The team used 2,207 images from 270 patients to train autoscoRA, 1,150 images from 133 patients for validation, and 1,834 images from 237 patients to test it.

The group had access to a high-quality data set of almost 6,000 hand radiographs from their institution, the result of foresight of principal investigator Daniel Aletaha, MD, and his predecessor Josef Smolen, MD. They “thought ahead and started collecting data and had all of it scored,” Dr. Deimel said. The work wasn’t all completed ahead of time, though. Dr. Deimel had to pull images from the hospital’s system sort through them manually.

The group also benefited from close proximity to computer scientists, including coauthor Georg Langs from the Medical University of Vienna’s computational imaging research lab. “We were lucky that we have a computer science department that is very much involved in medical imaging,” Dr. Deimel said.

The trained system successfully identified regions of interest in 96% of joints. It calculated the same score as the human reader in 80.5% of metacarpophalangeal joints and 72.3% of proximal interphalangeal joints. It deviated by more than 1 point from the gold-standard score in just 1.8% of metacarpophalangeal joints and 1.7% of proximal interphalangeal joints.

The researchers aim next to extend the program to bone erosions and also to images of the wrists and feet. They also hope to use scores from the program in clinical trials to measure a treatment’s effect, in registries of routine patient visits where thousands of such images along with clinical data could form the basis of informative observational studies, and in clinical practice, though likely with human oversight.

The study received no outside financial support. Dr. Deimel had no relevant financial disclosures. Mr. Langs reported being cofounder and shareholder of contextflow and receiving grants from Novartis, Siemens Healthineers, and NVIDIA. Dr. Aletaha reported financial relationships with many companies marketing drugs for rheumatoid arthritis.

SOURCE: Deimel T et al. Ann Rheum Dis. 2020 Jun;79(suppl 1):39-40.

A novel program that aims to automate the Sharp-van der Heijde scoring of radiographs of patients with rheumatoid arthritis has shown good reliability in identifying regions of interest and matching human reader scoring for joint-space narrowing, according to a report given at the annual European Congress of Rheumatology, held online this year because of COVID-19.

Courtesy Dr. Thomas Deimel

First author and presenter Thomas Deimel, MD, and colleagues at the Medical University of Vienna said their program, called autoscoRA, may be a solution to the problem of readers having to make subjective calls on the severity of damage seen on radiographs.

Although the work continues to be validated, Dr. Deimel, a resident at the university, is confident in the system as is. “I think for joint space narrowing, we’re there at the point where this could be used and could be as good as a human reader in terms of reliability,” he said in an interview. To find out, the group plans to compare the variability between autoscoRA and a gold-standard human reader against the variability seen between human readers. If the two measures of variability are similar, it would provide a strong endorsement.

The effort is far from the first to develop an automatic scoring system for RA images, but no fully automated system has emerged as reliable, according to Dr. Deimel. He thinks one main issue for others has been lack of access to a sufficient data set to train systems. It can be difficult to find enough training images because many types of joint damage are comparatively uncommon. The problem is made even worse because images can be hard to interpret: The shapes that the system must decipher can be misleading, especially in positions of tendon insertion or ligament attachment that can resemble damage. Differing angles of view between various training images can also complicate matters.

The autoscoRA program is based on modifications of a form of convolutional neural network called the VGG16 architecture. The team used 2,207 images from 270 patients to train autoscoRA, 1,150 images from 133 patients for validation, and 1,834 images from 237 patients to test it.

The group had access to a high-quality data set of almost 6,000 hand radiographs from their institution, the result of foresight of principal investigator Daniel Aletaha, MD, and his predecessor Josef Smolen, MD. They “thought ahead and started collecting data and had all of it scored,” Dr. Deimel said. The work wasn’t all completed ahead of time, though. Dr. Deimel had to pull images from the hospital’s system sort through them manually.

The group also benefited from close proximity to computer scientists, including coauthor Georg Langs from the Medical University of Vienna’s computational imaging research lab. “We were lucky that we have a computer science department that is very much involved in medical imaging,” Dr. Deimel said.

The trained system successfully identified regions of interest in 96% of joints. It calculated the same score as the human reader in 80.5% of metacarpophalangeal joints and 72.3% of proximal interphalangeal joints. It deviated by more than 1 point from the gold-standard score in just 1.8% of metacarpophalangeal joints and 1.7% of proximal interphalangeal joints.

The researchers aim next to extend the program to bone erosions and also to images of the wrists and feet. They also hope to use scores from the program in clinical trials to measure a treatment’s effect, in registries of routine patient visits where thousands of such images along with clinical data could form the basis of informative observational studies, and in clinical practice, though likely with human oversight.

The study received no outside financial support. Dr. Deimel had no relevant financial disclosures. Mr. Langs reported being cofounder and shareholder of contextflow and receiving grants from Novartis, Siemens Healthineers, and NVIDIA. Dr. Aletaha reported financial relationships with many companies marketing drugs for rheumatoid arthritis.

SOURCE: Deimel T et al. Ann Rheum Dis. 2020 Jun;79(suppl 1):39-40.

A novel program that aims to automate the Sharp-van der Heijde scoring of radiographs of patients with rheumatoid arthritis has shown good reliability in identifying regions of interest and matching human reader scoring for joint-space narrowing, according to a report given at the annual European Congress of Rheumatology, held online this year because of COVID-19.

Courtesy Dr. Thomas Deimel

First author and presenter Thomas Deimel, MD, and colleagues at the Medical University of Vienna said their program, called autoscoRA, may be a solution to the problem of readers having to make subjective calls on the severity of damage seen on radiographs.

Although the work continues to be validated, Dr. Deimel, a resident at the university, is confident in the system as is. “I think for joint space narrowing, we’re there at the point where this could be used and could be as good as a human reader in terms of reliability,” he said in an interview. To find out, the group plans to compare the variability between autoscoRA and a gold-standard human reader against the variability seen between human readers. If the two measures of variability are similar, it would provide a strong endorsement.

The effort is far from the first to develop an automatic scoring system for RA images, but no fully automated system has emerged as reliable, according to Dr. Deimel. He thinks one main issue for others has been lack of access to a sufficient data set to train systems. It can be difficult to find enough training images because many types of joint damage are comparatively uncommon. The problem is made even worse because images can be hard to interpret: The shapes that the system must decipher can be misleading, especially in positions of tendon insertion or ligament attachment that can resemble damage. Differing angles of view between various training images can also complicate matters.

The autoscoRA program is based on modifications of a form of convolutional neural network called the VGG16 architecture. The team used 2,207 images from 270 patients to train autoscoRA, 1,150 images from 133 patients for validation, and 1,834 images from 237 patients to test it.

The group had access to a high-quality data set of almost 6,000 hand radiographs from their institution, the result of foresight of principal investigator Daniel Aletaha, MD, and his predecessor Josef Smolen, MD. They “thought ahead and started collecting data and had all of it scored,” Dr. Deimel said. The work wasn’t all completed ahead of time, though. Dr. Deimel had to pull images from the hospital’s system sort through them manually.

The group also benefited from close proximity to computer scientists, including coauthor Georg Langs from the Medical University of Vienna’s computational imaging research lab. “We were lucky that we have a computer science department that is very much involved in medical imaging,” Dr. Deimel said.

The trained system successfully identified regions of interest in 96% of joints. It calculated the same score as the human reader in 80.5% of metacarpophalangeal joints and 72.3% of proximal interphalangeal joints. It deviated by more than 1 point from the gold-standard score in just 1.8% of metacarpophalangeal joints and 1.7% of proximal interphalangeal joints.

The researchers aim next to extend the program to bone erosions and also to images of the wrists and feet. They also hope to use scores from the program in clinical trials to measure a treatment’s effect, in registries of routine patient visits where thousands of such images along with clinical data could form the basis of informative observational studies, and in clinical practice, though likely with human oversight.

The study received no outside financial support. Dr. Deimel had no relevant financial disclosures. Mr. Langs reported being cofounder and shareholder of contextflow and receiving grants from Novartis, Siemens Healthineers, and NVIDIA. Dr. Aletaha reported financial relationships with many companies marketing drugs for rheumatoid arthritis.

SOURCE: Deimel T et al. Ann Rheum Dis. 2020 Jun;79(suppl 1):39-40.

ACE levels are lower in individuals with first episode psychosis (FEP) and even lower in those with resistant disease, suggesting the enzyme may be a biomarker of disease severity.

In a longitudinal cohort study, investigators found patients with FEP had significantly reduced ACE levels compared with their healthy peers.

With blood concentrations of the enzyme significantly reduced in those who were treatment-resistant, “ACE alterations appear to be already present at the disease onset” and results suggest “a possible relationship with disease severity,” noted the researchers, led by investigator Luisa Longo, MD, a resident in psychiatry, University of Bari Aldo Moro in Italy.

Moreover, the finding that lower ACE levels were associated with greater cognitive impairment on neuropsychological tests indicates the enzyme plays a role in “the alteration of neurocognitive abilities” in patients with FEP.

Taken together, the results “highlight ACE as a promising peripheral biomarker to identify patients at risk of treatment resistance to antipsychotics,” the investigators reported.

The findings were presented at the annual congress of the Schizophrenia International Research Society.
 

Mechanisms “poorly understood”

Previous studies suggest ACE may play a role in neurologic and psychiatric conditions, including schizophrenia, through alterations in function or blood concentrations.

However, the molecular mechanisms underlying disease onset and response to antipsychotics in patients with FEP “remain poorly understood,” the researchers noted. In addition, “despite adequate antipsychotic treatment, 20% of patients have persistent symptoms.”

To determine whether ACE levels are already altered in FEP patients, the investigators examined data on 138 patients with FEP and 115 healthy controls.

After measuring blood concentrations in 122 of the patients and 78 controls, they found that ACE levels were significantly lower in FEP patients (P = 4.1x10-13) after controlling for age, sex, ethnicity, duration of illness, smoking status, and chlorpromazine equivalents.

Cerebrospinal fluid (CSF) levels, which were measured in 19 patients and 18 controls, were also significantly lower in individuals with FEP (P = .01), with a strong correlation observed between blood and CSF levels (P = .0005).

Next, the team used Treatment Response and Resistance in Psychosis criteria to compare ACE levels in 32 treatment-resistant patients and 106 non–treatment-resistant patients. Results showed that ACE blood levels were significantly lower in the treatment-resistant patients (P = .03).

Finally, the association between ACE blood levels and range of clinical and neurocognitive variables were examined across all FEP patients.

The Scale for the Assessment of Negative and Positive Symptoms was administered, along with a battery of tests looking at processing speed, working memory, verbal learning and memory, visual learning and memory, ideational fluency, and executive function. All were combined into a composite score.

While there was no association between ACE blood levels and symptom severity in the patients, there was a significant association between levels and verbal memory (P = .007) and composite cognitive score (P = .04).
 

Notable finding

In an interview, Thomas W. Sedlak, MD, PhD, assistant professor of psychiatry and behavioral health, Johns Hopkins University, Baltimore, said the finding that ACE levels were associated with lower cognition scores is “notable in that we don’t really have any treatments for cognition.

“Antipsychotic drugs treat more of the famous symptoms of hallucinations and delusions and disordered speech, but they don›t really help cognition a whole lot — and too much medicine might even make that worse,” said Dr. Sedlak, who was not involved with the research.

“So it’s interesting to have another biomarker that might relate a symptom of schizophrenia that we don’t really have a good grip on addressing,” he said.

However, he noted that this study is “preliminary,” has not looked at longitudinal changes in ACE in the same patients, and is one of “many” correlation studies.

“I like to say you can pretty much Google any chemical in the body and somebody has a claim about it and schizophrenia,” Dr. Sedlak said.

Nevertheless, the current analysis is “convergent” with past studies on ACE, including those that have found associations between polymorphisms in the enzyme and schizophrenia, he noted.

Moreover, research has shown that ACE facilitates glutamate transmission, specifically via N-methyl-D-aspartate (NMDA) receptors in the prefrontal cortex, “which is probably the brain region most tied to schizophrenia abnormalities,” Dr. Sedlak said.
 

No tie to inflammation

The findings do contrast, however, with the increasing body of evidence linking schizophrenia to inflammation.

Dr. Sedlak said that is not surprising, as the more that is learned about schizophrenia, “the less it is likely to be a single homogeneous entity but something more akin to intellectual disability.

“We’re finding that there are different subtypes of schizophrenia, some of which might have more of an inflammatory tie and others which don’t.”

He added that it might be possible over the longer term to cluster patients by ACE levels and other biomarkers and then follow them long term to “see if we can predict outcomes better than purely clinical terms.”

In this way, Dr. Sedlak said he believes that psychiatry may become more like rheumatology, “which I’d say is the area of medicine, at least in terms of making diagnoses, most similar.”

The etiology of conditions such as lupus and rheumatoid arthritis is “not absolutely known” and there is “probably no single cause,” with the diagnosis relying on clinical findings alongside biomarker tests.

“I think psychiatry is, long term, hoping to discover some biomarkers ... that would be used together with the clinical findings to help come to more clinical agreement on how to define cases – and would be predictive long term in terms of the course of illness,” Dr. Sedlak concluded.

The study had no specific funding. The study investigators and Dr. Sedlak have disclosed no relevant financial relationships.
 

A version of this article originally appeared on Medscape.com.

ACE levels are lower in individuals with first episode psychosis (FEP) and even lower in those with resistant disease, suggesting the enzyme may be a biomarker of disease severity.

In a longitudinal cohort study, investigators found patients with FEP had significantly reduced ACE levels compared with their healthy peers.

With blood concentrations of the enzyme significantly reduced in those who were treatment-resistant, “ACE alterations appear to be already present at the disease onset” and results suggest “a possible relationship with disease severity,” noted the researchers, led by investigator Luisa Longo, MD, a resident in psychiatry, University of Bari Aldo Moro in Italy.

Moreover, the finding that lower ACE levels were associated with greater cognitive impairment on neuropsychological tests indicates the enzyme plays a role in “the alteration of neurocognitive abilities” in patients with FEP.

Taken together, the results “highlight ACE as a promising peripheral biomarker to identify patients at risk of treatment resistance to antipsychotics,” the investigators reported.

The findings were presented at the annual congress of the Schizophrenia International Research Society.
 

Mechanisms “poorly understood”

Previous studies suggest ACE may play a role in neurologic and psychiatric conditions, including schizophrenia, through alterations in function or blood concentrations.

However, the molecular mechanisms underlying disease onset and response to antipsychotics in patients with FEP “remain poorly understood,” the researchers noted. In addition, “despite adequate antipsychotic treatment, 20% of patients have persistent symptoms.”

To determine whether ACE levels are already altered in FEP patients, the investigators examined data on 138 patients with FEP and 115 healthy controls.

After measuring blood concentrations in 122 of the patients and 78 controls, they found that ACE levels were significantly lower in FEP patients (P = 4.1x10-13) after controlling for age, sex, ethnicity, duration of illness, smoking status, and chlorpromazine equivalents.

Cerebrospinal fluid (CSF) levels, which were measured in 19 patients and 18 controls, were also significantly lower in individuals with FEP (P = .01), with a strong correlation observed between blood and CSF levels (P = .0005).

Next, the team used Treatment Response and Resistance in Psychosis criteria to compare ACE levels in 32 treatment-resistant patients and 106 non–treatment-resistant patients. Results showed that ACE blood levels were significantly lower in the treatment-resistant patients (P = .03).

Finally, the association between ACE blood levels and range of clinical and neurocognitive variables were examined across all FEP patients.

The Scale for the Assessment of Negative and Positive Symptoms was administered, along with a battery of tests looking at processing speed, working memory, verbal learning and memory, visual learning and memory, ideational fluency, and executive function. All were combined into a composite score.

While there was no association between ACE blood levels and symptom severity in the patients, there was a significant association between levels and verbal memory (P = .007) and composite cognitive score (P = .04).
 

Notable finding

In an interview, Thomas W. Sedlak, MD, PhD, assistant professor of psychiatry and behavioral health, Johns Hopkins University, Baltimore, said the finding that ACE levels were associated with lower cognition scores is “notable in that we don’t really have any treatments for cognition.

“Antipsychotic drugs treat more of the famous symptoms of hallucinations and delusions and disordered speech, but they don›t really help cognition a whole lot — and too much medicine might even make that worse,” said Dr. Sedlak, who was not involved with the research.

“So it’s interesting to have another biomarker that might relate a symptom of schizophrenia that we don’t really have a good grip on addressing,” he said.

However, he noted that this study is “preliminary,” has not looked at longitudinal changes in ACE in the same patients, and is one of “many” correlation studies.

“I like to say you can pretty much Google any chemical in the body and somebody has a claim about it and schizophrenia,” Dr. Sedlak said.

Nevertheless, the current analysis is “convergent” with past studies on ACE, including those that have found associations between polymorphisms in the enzyme and schizophrenia, he noted.

Moreover, research has shown that ACE facilitates glutamate transmission, specifically via N-methyl-D-aspartate (NMDA) receptors in the prefrontal cortex, “which is probably the brain region most tied to schizophrenia abnormalities,” Dr. Sedlak said.
 

No tie to inflammation

The findings do contrast, however, with the increasing body of evidence linking schizophrenia to inflammation.

Dr. Sedlak said that is not surprising, as the more that is learned about schizophrenia, “the less it is likely to be a single homogeneous entity but something more akin to intellectual disability.

“We’re finding that there are different subtypes of schizophrenia, some of which might have more of an inflammatory tie and others which don’t.”

He added that it might be possible over the longer term to cluster patients by ACE levels and other biomarkers and then follow them long term to “see if we can predict outcomes better than purely clinical terms.”

In this way, Dr. Sedlak said he believes that psychiatry may become more like rheumatology, “which I’d say is the area of medicine, at least in terms of making diagnoses, most similar.”

The etiology of conditions such as lupus and rheumatoid arthritis is “not absolutely known” and there is “probably no single cause,” with the diagnosis relying on clinical findings alongside biomarker tests.

“I think psychiatry is, long term, hoping to discover some biomarkers ... that would be used together with the clinical findings to help come to more clinical agreement on how to define cases – and would be predictive long term in terms of the course of illness,” Dr. Sedlak concluded.

The study had no specific funding. The study investigators and Dr. Sedlak have disclosed no relevant financial relationships.
 

A version of this article originally appeared on Medscape.com.

ACE levels are lower in individuals with first episode psychosis (FEP) and even lower in those with resistant disease, suggesting the enzyme may be a biomarker of disease severity.

In a longitudinal cohort study, investigators found patients with FEP had significantly reduced ACE levels compared with their healthy peers.

With blood concentrations of the enzyme significantly reduced in those who were treatment-resistant, “ACE alterations appear to be already present at the disease onset” and results suggest “a possible relationship with disease severity,” noted the researchers, led by investigator Luisa Longo, MD, a resident in psychiatry, University of Bari Aldo Moro in Italy.

Moreover, the finding that lower ACE levels were associated with greater cognitive impairment on neuropsychological tests indicates the enzyme plays a role in “the alteration of neurocognitive abilities” in patients with FEP.

Taken together, the results “highlight ACE as a promising peripheral biomarker to identify patients at risk of treatment resistance to antipsychotics,” the investigators reported.

The findings were presented at the annual congress of the Schizophrenia International Research Society.
 

Mechanisms “poorly understood”

Previous studies suggest ACE may play a role in neurologic and psychiatric conditions, including schizophrenia, through alterations in function or blood concentrations.

However, the molecular mechanisms underlying disease onset and response to antipsychotics in patients with FEP “remain poorly understood,” the researchers noted. In addition, “despite adequate antipsychotic treatment, 20% of patients have persistent symptoms.”

To determine whether ACE levels are already altered in FEP patients, the investigators examined data on 138 patients with FEP and 115 healthy controls.

After measuring blood concentrations in 122 of the patients and 78 controls, they found that ACE levels were significantly lower in FEP patients (P = 4.1x10-13) after controlling for age, sex, ethnicity, duration of illness, smoking status, and chlorpromazine equivalents.

Cerebrospinal fluid (CSF) levels, which were measured in 19 patients and 18 controls, were also significantly lower in individuals with FEP (P = .01), with a strong correlation observed between blood and CSF levels (P = .0005).

Next, the team used Treatment Response and Resistance in Psychosis criteria to compare ACE levels in 32 treatment-resistant patients and 106 non–treatment-resistant patients. Results showed that ACE blood levels were significantly lower in the treatment-resistant patients (P = .03).

Finally, the association between ACE blood levels and range of clinical and neurocognitive variables were examined across all FEP patients.

The Scale for the Assessment of Negative and Positive Symptoms was administered, along with a battery of tests looking at processing speed, working memory, verbal learning and memory, visual learning and memory, ideational fluency, and executive function. All were combined into a composite score.

While there was no association between ACE blood levels and symptom severity in the patients, there was a significant association between levels and verbal memory (P = .007) and composite cognitive score (P = .04).
 

Notable finding

In an interview, Thomas W. Sedlak, MD, PhD, assistant professor of psychiatry and behavioral health, Johns Hopkins University, Baltimore, said the finding that ACE levels were associated with lower cognition scores is “notable in that we don’t really have any treatments for cognition.

“Antipsychotic drugs treat more of the famous symptoms of hallucinations and delusions and disordered speech, but they don›t really help cognition a whole lot — and too much medicine might even make that worse,” said Dr. Sedlak, who was not involved with the research.

“So it’s interesting to have another biomarker that might relate a symptom of schizophrenia that we don’t really have a good grip on addressing,” he said.

However, he noted that this study is “preliminary,” has not looked at longitudinal changes in ACE in the same patients, and is one of “many” correlation studies.

“I like to say you can pretty much Google any chemical in the body and somebody has a claim about it and schizophrenia,” Dr. Sedlak said.

Nevertheless, the current analysis is “convergent” with past studies on ACE, including those that have found associations between polymorphisms in the enzyme and schizophrenia, he noted.

Moreover, research has shown that ACE facilitates glutamate transmission, specifically via N-methyl-D-aspartate (NMDA) receptors in the prefrontal cortex, “which is probably the brain region most tied to schizophrenia abnormalities,” Dr. Sedlak said.
 

No tie to inflammation

The findings do contrast, however, with the increasing body of evidence linking schizophrenia to inflammation.

Dr. Sedlak said that is not surprising, as the more that is learned about schizophrenia, “the less it is likely to be a single homogeneous entity but something more akin to intellectual disability.

“We’re finding that there are different subtypes of schizophrenia, some of which might have more of an inflammatory tie and others which don’t.”

He added that it might be possible over the longer term to cluster patients by ACE levels and other biomarkers and then follow them long term to “see if we can predict outcomes better than purely clinical terms.”

In this way, Dr. Sedlak said he believes that psychiatry may become more like rheumatology, “which I’d say is the area of medicine, at least in terms of making diagnoses, most similar.”

The etiology of conditions such as lupus and rheumatoid arthritis is “not absolutely known” and there is “probably no single cause,” with the diagnosis relying on clinical findings alongside biomarker tests.

“I think psychiatry is, long term, hoping to discover some biomarkers ... that would be used together with the clinical findings to help come to more clinical agreement on how to define cases – and would be predictive long term in terms of the course of illness,” Dr. Sedlak concluded.

The study had no specific funding. The study investigators and Dr. Sedlak have disclosed no relevant financial relationships.
 

A version of this article originally appeared on Medscape.com.

Targeting TIGIT, an inhibitory receptor expressed on immune cells, could complement activity of anti–programmed death–ligand 1/PD-1 antibodies in patients with solid tumors, results of a phase 1 study suggest.

The combination of the anti-TIGIT antibody tiragolumab with the PD-L1 inhibitor atezolizumab was well tolerated and showed preliminary activity in the phase 1b portion of the study, according to investigator Johanna C. Bendell, MD, of Sarah Cannon Research Institute/Tennessee Oncology in Nashville, Tenn.

Objective responses occurred mainly in chemoimmunotherapy-naive, PD-L1-positive tumors. In an expansion cohort of 13 patients with PD-L1-positive non–small cell lung cancer (NSCLC), the confirmed overall response rate was 46%, with several responses demonstrating durability.

Dr. Bendell reported these results at the AACR virtual meeting II.

While several important research questions remain, the results in the lung cancer expansion cohort were encouraging, particularly in patients who were smokers and previous smokers, said invited discussant Michele Teng, PhD, of QIMR Berghofer Medical Research Institute in Brisbane, Australia.

“Although it was [a] small cohort, the data suggest promising duration of response in some of the patients [n = 4] who have been under study for more than 700 days,” Dr. Teng said.

Based on the preliminary safety and activity seen in this study, the combination of tiragolumab and atezolizumab is being evaluated in a randomized, placebo-controlled phase 2 study, and a phase 3 study is recruiting.
 

Rationale, design, and safety

TIGIT is a novel inhibitory receptor expressed on multiple immune cells, especially CD8-positive T cells and natural killer cells, Dr. Bendell explained. She added that TIGIT is coexpressed with PD-1 on immune cells.

“Using anti-TIGIT antibodies to prevent TIGIT from binding, and cotargeting TIGIT and PD-L1, may restore antitumor response and enhance anti-PD-L1 effect,” Dr. Bendell said.

The phase 1 study Dr. Bendell presented, known as GO30103, was designed to evaluate tiragolumab as a single agent and in combination with atezolizumab in advanced solid tumors.

There were 24 patients in the phase 1a portion of GO30103, which was intended to determine the preliminary safety, tolerability, and recommended phase 2 dose of tiragolumab. There were 49 patients treated with tiragolumab plus atezolizumab in the phase 1b portion, which was intended to provide data on pharmacokinetics as well as preliminary antitumor activity of the combination.

No dose-limiting toxicities were seen in either cohort. The recommended phase 2 dose of tiragolumab was 600 mg every 3 weeks.

Tiragolumab was well tolerated in the phase 1a and 1b portions of the trial, according to Dr. Bendell.

“Immune-related adverse events were seen, but their incidence was not out of proportion to events seen with atezolizumab alone,” she said.

Treatment-related grade 3-4 adverse events occurred in one patient (4%) in the phase 1a portion of the trial and two patients (4%) in the phase 1b portion. There were no grade 5 adverse events related to treatment.

Efficacy and next steps

No objective responses were seen with tiragolumab monotherapy, although several patients did exhibit tumor reduction.

“We were not really expecting much single-agent activity of the anti-TIGIT drug,” Dr. Bendell said. “There’s some preclinical data that suggests that TIGIT may be more important as a single agent in earlier stages of cancer.”

In contrast, the combination of tiragolumab and atezolizumab resulted in several responses, including one in a patient with PD-L1-positive NSCLC who was previously treated with immunotherapy, according to Dr. Bendell.

The 13-patient expansion cohort of patients with PD-L1-positive NSCLC were treated at the recommended phase 2 dose of tiragolumab and atezolizumab. In these chemoimmunotherapy-naive patients, the overall response rate was 46%. Responses occurred in 6 of 13 patients and included 2 complete responses. Four patients had stable disease, so the disease control rate was 85% (11/13).

Based on that expansion cohort, a randomized, phase 2 study called CITYSCAPE was initiated. Results of CITYSCAPE were recently presented as part of the American Society of Clinical Oncology virtual scientific program.

In that study, tiragolumab plus atezolizumab improved the overall response rate and progression-free survival when compared with placebo plus atezolizumab. More substantial improvement was seen in the subgroup of patients with PD-L1 tumor proportion scores of 50% or greater.

The activity and safety of tiragolumab plus atezolizumab will be confirmed in the ongoing SKYSCRAPER-01 trial (NCT04294810), a phase 3 study of first-line treatment in patients with NSCLC and a PD-L1 tumor proportion score of 50% or greater, according to investigators.

The phase 1 study presented by Dr. Bendell was sponsored by Genentech. Dr. Bendell disclosed relationships with Genentech/Roche, Gilead, Five Prime, Lilly, and other companies.
 

SOURCE: Bendell JC et al. AACR 2020, Abstract CT302.

Targeting TIGIT, an inhibitory receptor expressed on immune cells, could complement activity of anti–programmed death–ligand 1/PD-1 antibodies in patients with solid tumors, results of a phase 1 study suggest.

The combination of the anti-TIGIT antibody tiragolumab with the PD-L1 inhibitor atezolizumab was well tolerated and showed preliminary activity in the phase 1b portion of the study, according to investigator Johanna C. Bendell, MD, of Sarah Cannon Research Institute/Tennessee Oncology in Nashville, Tenn.

Objective responses occurred mainly in chemoimmunotherapy-naive, PD-L1-positive tumors. In an expansion cohort of 13 patients with PD-L1-positive non–small cell lung cancer (NSCLC), the confirmed overall response rate was 46%, with several responses demonstrating durability.

Dr. Bendell reported these results at the AACR virtual meeting II.

While several important research questions remain, the results in the lung cancer expansion cohort were encouraging, particularly in patients who were smokers and previous smokers, said invited discussant Michele Teng, PhD, of QIMR Berghofer Medical Research Institute in Brisbane, Australia.

“Although it was [a] small cohort, the data suggest promising duration of response in some of the patients [n = 4] who have been under study for more than 700 days,” Dr. Teng said.

Based on the preliminary safety and activity seen in this study, the combination of tiragolumab and atezolizumab is being evaluated in a randomized, placebo-controlled phase 2 study, and a phase 3 study is recruiting.
 

Rationale, design, and safety

TIGIT is a novel inhibitory receptor expressed on multiple immune cells, especially CD8-positive T cells and natural killer cells, Dr. Bendell explained. She added that TIGIT is coexpressed with PD-1 on immune cells.

“Using anti-TIGIT antibodies to prevent TIGIT from binding, and cotargeting TIGIT and PD-L1, may restore antitumor response and enhance anti-PD-L1 effect,” Dr. Bendell said.

The phase 1 study Dr. Bendell presented, known as GO30103, was designed to evaluate tiragolumab as a single agent and in combination with atezolizumab in advanced solid tumors.

There were 24 patients in the phase 1a portion of GO30103, which was intended to determine the preliminary safety, tolerability, and recommended phase 2 dose of tiragolumab. There were 49 patients treated with tiragolumab plus atezolizumab in the phase 1b portion, which was intended to provide data on pharmacokinetics as well as preliminary antitumor activity of the combination.

No dose-limiting toxicities were seen in either cohort. The recommended phase 2 dose of tiragolumab was 600 mg every 3 weeks.

Tiragolumab was well tolerated in the phase 1a and 1b portions of the trial, according to Dr. Bendell.

“Immune-related adverse events were seen, but their incidence was not out of proportion to events seen with atezolizumab alone,” she said.

Treatment-related grade 3-4 adverse events occurred in one patient (4%) in the phase 1a portion of the trial and two patients (4%) in the phase 1b portion. There were no grade 5 adverse events related to treatment.

Efficacy and next steps

No objective responses were seen with tiragolumab monotherapy, although several patients did exhibit tumor reduction.

“We were not really expecting much single-agent activity of the anti-TIGIT drug,” Dr. Bendell said. “There’s some preclinical data that suggests that TIGIT may be more important as a single agent in earlier stages of cancer.”

In contrast, the combination of tiragolumab and atezolizumab resulted in several responses, including one in a patient with PD-L1-positive NSCLC who was previously treated with immunotherapy, according to Dr. Bendell.

The 13-patient expansion cohort of patients with PD-L1-positive NSCLC were treated at the recommended phase 2 dose of tiragolumab and atezolizumab. In these chemoimmunotherapy-naive patients, the overall response rate was 46%. Responses occurred in 6 of 13 patients and included 2 complete responses. Four patients had stable disease, so the disease control rate was 85% (11/13).

Based on that expansion cohort, a randomized, phase 2 study called CITYSCAPE was initiated. Results of CITYSCAPE were recently presented as part of the American Society of Clinical Oncology virtual scientific program.

In that study, tiragolumab plus atezolizumab improved the overall response rate and progression-free survival when compared with placebo plus atezolizumab. More substantial improvement was seen in the subgroup of patients with PD-L1 tumor proportion scores of 50% or greater.

The activity and safety of tiragolumab plus atezolizumab will be confirmed in the ongoing SKYSCRAPER-01 trial (NCT04294810), a phase 3 study of first-line treatment in patients with NSCLC and a PD-L1 tumor proportion score of 50% or greater, according to investigators.

The phase 1 study presented by Dr. Bendell was sponsored by Genentech. Dr. Bendell disclosed relationships with Genentech/Roche, Gilead, Five Prime, Lilly, and other companies.
 

SOURCE: Bendell JC et al. AACR 2020, Abstract CT302.

Targeting TIGIT, an inhibitory receptor expressed on immune cells, could complement activity of anti–programmed death–ligand 1/PD-1 antibodies in patients with solid tumors, results of a phase 1 study suggest.

The combination of the anti-TIGIT antibody tiragolumab with the PD-L1 inhibitor atezolizumab was well tolerated and showed preliminary activity in the phase 1b portion of the study, according to investigator Johanna C. Bendell, MD, of Sarah Cannon Research Institute/Tennessee Oncology in Nashville, Tenn.

Objective responses occurred mainly in chemoimmunotherapy-naive, PD-L1-positive tumors. In an expansion cohort of 13 patients with PD-L1-positive non–small cell lung cancer (NSCLC), the confirmed overall response rate was 46%, with several responses demonstrating durability.

Dr. Bendell reported these results at the AACR virtual meeting II.

While several important research questions remain, the results in the lung cancer expansion cohort were encouraging, particularly in patients who were smokers and previous smokers, said invited discussant Michele Teng, PhD, of QIMR Berghofer Medical Research Institute in Brisbane, Australia.

“Although it was [a] small cohort, the data suggest promising duration of response in some of the patients [n = 4] who have been under study for more than 700 days,” Dr. Teng said.

Based on the preliminary safety and activity seen in this study, the combination of tiragolumab and atezolizumab is being evaluated in a randomized, placebo-controlled phase 2 study, and a phase 3 study is recruiting.
 

Rationale, design, and safety

TIGIT is a novel inhibitory receptor expressed on multiple immune cells, especially CD8-positive T cells and natural killer cells, Dr. Bendell explained. She added that TIGIT is coexpressed with PD-1 on immune cells.

“Using anti-TIGIT antibodies to prevent TIGIT from binding, and cotargeting TIGIT and PD-L1, may restore antitumor response and enhance anti-PD-L1 effect,” Dr. Bendell said.

The phase 1 study Dr. Bendell presented, known as GO30103, was designed to evaluate tiragolumab as a single agent and in combination with atezolizumab in advanced solid tumors.

There were 24 patients in the phase 1a portion of GO30103, which was intended to determine the preliminary safety, tolerability, and recommended phase 2 dose of tiragolumab. There were 49 patients treated with tiragolumab plus atezolizumab in the phase 1b portion, which was intended to provide data on pharmacokinetics as well as preliminary antitumor activity of the combination.

No dose-limiting toxicities were seen in either cohort. The recommended phase 2 dose of tiragolumab was 600 mg every 3 weeks.

Tiragolumab was well tolerated in the phase 1a and 1b portions of the trial, according to Dr. Bendell.

“Immune-related adverse events were seen, but their incidence was not out of proportion to events seen with atezolizumab alone,” she said.

Treatment-related grade 3-4 adverse events occurred in one patient (4%) in the phase 1a portion of the trial and two patients (4%) in the phase 1b portion. There were no grade 5 adverse events related to treatment.

Efficacy and next steps

No objective responses were seen with tiragolumab monotherapy, although several patients did exhibit tumor reduction.

“We were not really expecting much single-agent activity of the anti-TIGIT drug,” Dr. Bendell said. “There’s some preclinical data that suggests that TIGIT may be more important as a single agent in earlier stages of cancer.”

In contrast, the combination of tiragolumab and atezolizumab resulted in several responses, including one in a patient with PD-L1-positive NSCLC who was previously treated with immunotherapy, according to Dr. Bendell.

The 13-patient expansion cohort of patients with PD-L1-positive NSCLC were treated at the recommended phase 2 dose of tiragolumab and atezolizumab. In these chemoimmunotherapy-naive patients, the overall response rate was 46%. Responses occurred in 6 of 13 patients and included 2 complete responses. Four patients had stable disease, so the disease control rate was 85% (11/13).

Based on that expansion cohort, a randomized, phase 2 study called CITYSCAPE was initiated. Results of CITYSCAPE were recently presented as part of the American Society of Clinical Oncology virtual scientific program.

In that study, tiragolumab plus atezolizumab improved the overall response rate and progression-free survival when compared with placebo plus atezolizumab. More substantial improvement was seen in the subgroup of patients with PD-L1 tumor proportion scores of 50% or greater.

The activity and safety of tiragolumab plus atezolizumab will be confirmed in the ongoing SKYSCRAPER-01 trial (NCT04294810), a phase 3 study of first-line treatment in patients with NSCLC and a PD-L1 tumor proportion score of 50% or greater, according to investigators.

The phase 1 study presented by Dr. Bendell was sponsored by Genentech. Dr. Bendell disclosed relationships with Genentech/Roche, Gilead, Five Prime, Lilly, and other companies.
 

SOURCE: Bendell JC et al. AACR 2020, Abstract CT302.

A new visualization tool aims to streamline patient-clinician communication about risk factors for progression from episodic to chronic migraines. The tool is still in the prototype stage, but it could eventually synthesize patient responses to an integrated questionnaire and produce a chart illustrating where the patient stands with respect to a range of modifiable risk factors, including depression, medication overuse, insomnia, and body mass index, among others.

A few such tools exist for other conditions, such as stroke and risk of developing chronic diseases. Existing migraine visualization models focus only on individual risk factors, but they are capable of much more. “Visualization tools can effectively communicate a huge amount of clinical information,” said lead author Ami Cuneo, MD, who is a headache fellow at the University of Washington, Seattle, in an interview. Dr. Cuneo presented a poster describing the concept at the virtual annual meeting of the American Headache Society.
 

A picture is worth a thousand words

Dr. Cuneo’s background is well suited to the effort: Before entering medicine, she was a documentary producer. “I have a lot of interest in the patient story and history,” she added. She also believes that the tool could improve patient-provider relationships. In rushed sessions, patients may not feel heard. Patients gain a therapeutic benefit from the belief that their provider is listening to them and listening to their story. Visualization tools could promote that if the provider can quickly identify key elements of the patient’s condition. “A lot of headache patients can have a complex picture,” said Dr. Cuneo.

Physicians must see patients in short appointment periods, making it difficult to communicate all of the risk factors and behavioral characteristics that can contribute to risk of progression. “If you have a patient and you’re able to look at a visualization tool quickly and say: ‘Okay, my patient really is having insomnia and sleep issues,’ you can focus the session talking about sleep, cognitive-behavioral therapy for insomnia, and all the things we can help patients with,” said Dr. Cuneo.

The prototype visualization tool uses a color-coded wheel divided into pie slices, each representing a clinical characteristic or modifiable risk factor. In the proposed tool presented in the poster, these included depression, anxiety, functional disability, insomnia, nausea, headache frequency, medication overuse, optimization of abortive medication use, nontherapeutic diet, limited exercise, and body mass index range. The circle also contains colored concentric circles, ranging from red to green, and a small filled circle represents the patient’s status in each category as ranked using the integrated questionnaire. A line connects the circles in each pie, revealing the patient’s overall status.

The visual cue allows both the physician and patient to quickly assess these factors and see them in relationship to one another. Verbally communicating each factor is time consuming and harder for the patient to take in, according to Dr. Cuneo. “The provider can just look at it and see the areas to focus questions on to try to improve care. So it’s a way I’m hopeful that we can help target visits and improve patient-provider communication without extending visit time.”

A key challenge for the project will be choosing and consolidating scales so that the patient isn’t burdened with too many questions in advance of the appointment. The team will draw from existing scales and then create their own and validate it. “The questions will have to be vetted with patients through focus groups, and then the software platform [will have to be developed] so that patients can complete the survey online. Then we have to test it to see if providers and patients feel this is something that’s helpful in the clinical practice,” said Dr. Cuneo.
 

Will it change behavior?

If successful, the tool would be a welcome addition, according to Andrew Charles, MD, who was asked to comment on the work. “Epidemiological studies have identified these risk factors, but we haven’t had a way of operationalizing a strategy to reduce them systematically, so having some sort of tool that visualizes not just one but multiple risk factors is something I think could be helpful to address those factors more aggressively. The real question would be, if you put it in the hands of practitioners and patients, will they really be able to easily implement it and will it change behavior,” said Dr. Charles, who is a professor of neurology and director of the Goldberg Migraine Program at the University of California, Los Angeles.

The study received no funding. Dr. Cuneo and Dr. Charles have no relevant financial disclosures.

SOURCE; Cuneo A et al. AHS 2020, Abstract 273715.

A new visualization tool aims to streamline patient-clinician communication about risk factors for progression from episodic to chronic migraines. The tool is still in the prototype stage, but it could eventually synthesize patient responses to an integrated questionnaire and produce a chart illustrating where the patient stands with respect to a range of modifiable risk factors, including depression, medication overuse, insomnia, and body mass index, among others.

A few such tools exist for other conditions, such as stroke and risk of developing chronic diseases. Existing migraine visualization models focus only on individual risk factors, but they are capable of much more. “Visualization tools can effectively communicate a huge amount of clinical information,” said lead author Ami Cuneo, MD, who is a headache fellow at the University of Washington, Seattle, in an interview. Dr. Cuneo presented a poster describing the concept at the virtual annual meeting of the American Headache Society.
 

A picture is worth a thousand words

Dr. Cuneo’s background is well suited to the effort: Before entering medicine, she was a documentary producer. “I have a lot of interest in the patient story and history,” she added. She also believes that the tool could improve patient-provider relationships. In rushed sessions, patients may not feel heard. Patients gain a therapeutic benefit from the belief that their provider is listening to them and listening to their story. Visualization tools could promote that if the provider can quickly identify key elements of the patient’s condition. “A lot of headache patients can have a complex picture,” said Dr. Cuneo.

Physicians must see patients in short appointment periods, making it difficult to communicate all of the risk factors and behavioral characteristics that can contribute to risk of progression. “If you have a patient and you’re able to look at a visualization tool quickly and say: ‘Okay, my patient really is having insomnia and sleep issues,’ you can focus the session talking about sleep, cognitive-behavioral therapy for insomnia, and all the things we can help patients with,” said Dr. Cuneo.

The prototype visualization tool uses a color-coded wheel divided into pie slices, each representing a clinical characteristic or modifiable risk factor. In the proposed tool presented in the poster, these included depression, anxiety, functional disability, insomnia, nausea, headache frequency, medication overuse, optimization of abortive medication use, nontherapeutic diet, limited exercise, and body mass index range. The circle also contains colored concentric circles, ranging from red to green, and a small filled circle represents the patient’s status in each category as ranked using the integrated questionnaire. A line connects the circles in each pie, revealing the patient’s overall status.

The visual cue allows both the physician and patient to quickly assess these factors and see them in relationship to one another. Verbally communicating each factor is time consuming and harder for the patient to take in, according to Dr. Cuneo. “The provider can just look at it and see the areas to focus questions on to try to improve care. So it’s a way I’m hopeful that we can help target visits and improve patient-provider communication without extending visit time.”

A key challenge for the project will be choosing and consolidating scales so that the patient isn’t burdened with too many questions in advance of the appointment. The team will draw from existing scales and then create their own and validate it. “The questions will have to be vetted with patients through focus groups, and then the software platform [will have to be developed] so that patients can complete the survey online. Then we have to test it to see if providers and patients feel this is something that’s helpful in the clinical practice,” said Dr. Cuneo.
 

Will it change behavior?

If successful, the tool would be a welcome addition, according to Andrew Charles, MD, who was asked to comment on the work. “Epidemiological studies have identified these risk factors, but we haven’t had a way of operationalizing a strategy to reduce them systematically, so having some sort of tool that visualizes not just one but multiple risk factors is something I think could be helpful to address those factors more aggressively. The real question would be, if you put it in the hands of practitioners and patients, will they really be able to easily implement it and will it change behavior,” said Dr. Charles, who is a professor of neurology and director of the Goldberg Migraine Program at the University of California, Los Angeles.

The study received no funding. Dr. Cuneo and Dr. Charles have no relevant financial disclosures.

SOURCE; Cuneo A et al. AHS 2020, Abstract 273715.

A new visualization tool aims to streamline patient-clinician communication about risk factors for progression from episodic to chronic migraines. The tool is still in the prototype stage, but it could eventually synthesize patient responses to an integrated questionnaire and produce a chart illustrating where the patient stands with respect to a range of modifiable risk factors, including depression, medication overuse, insomnia, and body mass index, among others.

A few such tools exist for other conditions, such as stroke and risk of developing chronic diseases. Existing migraine visualization models focus only on individual risk factors, but they are capable of much more. “Visualization tools can effectively communicate a huge amount of clinical information,” said lead author Ami Cuneo, MD, who is a headache fellow at the University of Washington, Seattle, in an interview. Dr. Cuneo presented a poster describing the concept at the virtual annual meeting of the American Headache Society.
 

A picture is worth a thousand words

Dr. Cuneo’s background is well suited to the effort: Before entering medicine, she was a documentary producer. “I have a lot of interest in the patient story and history,” she added. She also believes that the tool could improve patient-provider relationships. In rushed sessions, patients may not feel heard. Patients gain a therapeutic benefit from the belief that their provider is listening to them and listening to their story. Visualization tools could promote that if the provider can quickly identify key elements of the patient’s condition. “A lot of headache patients can have a complex picture,” said Dr. Cuneo.

Physicians must see patients in short appointment periods, making it difficult to communicate all of the risk factors and behavioral characteristics that can contribute to risk of progression. “If you have a patient and you’re able to look at a visualization tool quickly and say: ‘Okay, my patient really is having insomnia and sleep issues,’ you can focus the session talking about sleep, cognitive-behavioral therapy for insomnia, and all the things we can help patients with,” said Dr. Cuneo.

The prototype visualization tool uses a color-coded wheel divided into pie slices, each representing a clinical characteristic or modifiable risk factor. In the proposed tool presented in the poster, these included depression, anxiety, functional disability, insomnia, nausea, headache frequency, medication overuse, optimization of abortive medication use, nontherapeutic diet, limited exercise, and body mass index range. The circle also contains colored concentric circles, ranging from red to green, and a small filled circle represents the patient’s status in each category as ranked using the integrated questionnaire. A line connects the circles in each pie, revealing the patient’s overall status.

The visual cue allows both the physician and patient to quickly assess these factors and see them in relationship to one another. Verbally communicating each factor is time consuming and harder for the patient to take in, according to Dr. Cuneo. “The provider can just look at it and see the areas to focus questions on to try to improve care. So it’s a way I’m hopeful that we can help target visits and improve patient-provider communication without extending visit time.”

A key challenge for the project will be choosing and consolidating scales so that the patient isn’t burdened with too many questions in advance of the appointment. The team will draw from existing scales and then create their own and validate it. “The questions will have to be vetted with patients through focus groups, and then the software platform [will have to be developed] so that patients can complete the survey online. Then we have to test it to see if providers and patients feel this is something that’s helpful in the clinical practice,” said Dr. Cuneo.
 

Will it change behavior?

If successful, the tool would be a welcome addition, according to Andrew Charles, MD, who was asked to comment on the work. “Epidemiological studies have identified these risk factors, but we haven’t had a way of operationalizing a strategy to reduce them systematically, so having some sort of tool that visualizes not just one but multiple risk factors is something I think could be helpful to address those factors more aggressively. The real question would be, if you put it in the hands of practitioners and patients, will they really be able to easily implement it and will it change behavior,” said Dr. Charles, who is a professor of neurology and director of the Goldberg Migraine Program at the University of California, Los Angeles.

The study received no funding. Dr. Cuneo and Dr. Charles have no relevant financial disclosures.

SOURCE; Cuneo A et al. AHS 2020, Abstract 273715.

There are at least five dermatologic patterns in patients who are suspected or confirmed of having COVID-19, and the knowledge base continues to evolve, according to Christine Ko, MD.

“Things are very fluid,” Dr. Ko, professor of dermatology and pathology at Yale University, New Haven, Conn., said during the virtual annual meeting of the American Academy of Dermatology. “New studies are coming out daily. Due to the need for rapid dissemination, a lot of the studies are case reports, but there are some nice case series. Another caveat for the literature is that a lot of these cases were not necessarily confirmed with testing for SARS-CoV-2, but some were.”

Dr. Ko framed her remarks largely on a case collection survey of images and clinical data from 375 patients in Spain with suspected or confirmed COVID-19 that was published online April 29, 2020, in the British Journal of Dermatology (doi: 10.1111/bjd.19163). Cutaneous manifestations included early vesicular eruptions mainly on the trunk or limbs (9%), maculopapular (47%) to urticarial lesions (19%) mainly on the trunk, and acral areas of erythema sometimes with vesicles or erosion (perniosis-like) (19%) that seemed to be a later manifestation of COVID-19. Retiform purpura or necrosis (6%) was most concerning in terms of skin disease, with an associated with a mortality of 10%.

On histology, the early vesicular eruptions are typically marked by dyskeratotic keratinocytes, Dr. Ko said, while urticarial lesions are characterized by a mixed dermal infiltrate; maculopapular lesions were a broad category. “There are some case reports that show spongiotic dermatitis or parakeratosis with a lymphocytic infiltrate,” she said. “A caveat to keep in mind is that, although these patients may definitely have COVID-19 and be confirmed to have it by testing, hypersensitivity reactions may be due to the multiple medications they’re on.”

Patients can develop a spectrum of lesions that are suggestive of vascular damage or occlusion, Dr. Ko continued. Livedoid lesions may remain static and not eventuate into necrosis or purpura but will self-resolve. Purpuric lesions and acral gangrene have been described, and these lesions correspond to vascular occlusion on biopsy.

A later manifestation are the so-called “COVID toes” with a superficial and deep lymphocytic infiltrate, as published June 1, 2020, in JAAD Case Reports: (doi: 10.1016/j.jdcr.2020.04.011).

“There are patients in the literature that have slightly different pathology, with lymphocytic inflammation as well as occlusion of vessels,” Dr. Ko said. A paper published June 20, 2020, in the British Journal of Dermatology used immunohistochemical staining against the SARS-CoV-2 spike protein, and biopsies of “COVID toes” had positive staining of endothelial cells, supporting the notion that “COVID toes” are a direct manifestation of viral infection (doi: 10.1111/bjd.19327).

“There’s a lot that we still don’t know, and some patterns are going to be outliers,” Dr. Ko concluded. “[As for] determining which skin manifestations are directly from coronavirus infection within the skin, more study is needed and likely time will tell.” She reported having no financial disclosures relevant to her talk.

dbrunk@mdedge.com

There are at least five dermatologic patterns in patients who are suspected or confirmed of having COVID-19, and the knowledge base continues to evolve, according to Christine Ko, MD.

“Things are very fluid,” Dr. Ko, professor of dermatology and pathology at Yale University, New Haven, Conn., said during the virtual annual meeting of the American Academy of Dermatology. “New studies are coming out daily. Due to the need for rapid dissemination, a lot of the studies are case reports, but there are some nice case series. Another caveat for the literature is that a lot of these cases were not necessarily confirmed with testing for SARS-CoV-2, but some were.”

Dr. Ko framed her remarks largely on a case collection survey of images and clinical data from 375 patients in Spain with suspected or confirmed COVID-19 that was published online April 29, 2020, in the British Journal of Dermatology (doi: 10.1111/bjd.19163). Cutaneous manifestations included early vesicular eruptions mainly on the trunk or limbs (9%), maculopapular (47%) to urticarial lesions (19%) mainly on the trunk, and acral areas of erythema sometimes with vesicles or erosion (perniosis-like) (19%) that seemed to be a later manifestation of COVID-19. Retiform purpura or necrosis (6%) was most concerning in terms of skin disease, with an associated with a mortality of 10%.

On histology, the early vesicular eruptions are typically marked by dyskeratotic keratinocytes, Dr. Ko said, while urticarial lesions are characterized by a mixed dermal infiltrate; maculopapular lesions were a broad category. “There are some case reports that show spongiotic dermatitis or parakeratosis with a lymphocytic infiltrate,” she said. “A caveat to keep in mind is that, although these patients may definitely have COVID-19 and be confirmed to have it by testing, hypersensitivity reactions may be due to the multiple medications they’re on.”

Patients can develop a spectrum of lesions that are suggestive of vascular damage or occlusion, Dr. Ko continued. Livedoid lesions may remain static and not eventuate into necrosis or purpura but will self-resolve. Purpuric lesions and acral gangrene have been described, and these lesions correspond to vascular occlusion on biopsy.

A later manifestation are the so-called “COVID toes” with a superficial and deep lymphocytic infiltrate, as published June 1, 2020, in JAAD Case Reports: (doi: 10.1016/j.jdcr.2020.04.011).

“There are patients in the literature that have slightly different pathology, with lymphocytic inflammation as well as occlusion of vessels,” Dr. Ko said. A paper published June 20, 2020, in the British Journal of Dermatology used immunohistochemical staining against the SARS-CoV-2 spike protein, and biopsies of “COVID toes” had positive staining of endothelial cells, supporting the notion that “COVID toes” are a direct manifestation of viral infection (doi: 10.1111/bjd.19327).

“There’s a lot that we still don’t know, and some patterns are going to be outliers,” Dr. Ko concluded. “[As for] determining which skin manifestations are directly from coronavirus infection within the skin, more study is needed and likely time will tell.” She reported having no financial disclosures relevant to her talk.

dbrunk@mdedge.com

There are at least five dermatologic patterns in patients who are suspected or confirmed of having COVID-19, and the knowledge base continues to evolve, according to Christine Ko, MD.

“Things are very fluid,” Dr. Ko, professor of dermatology and pathology at Yale University, New Haven, Conn., said during the virtual annual meeting of the American Academy of Dermatology. “New studies are coming out daily. Due to the need for rapid dissemination, a lot of the studies are case reports, but there are some nice case series. Another caveat for the literature is that a lot of these cases were not necessarily confirmed with testing for SARS-CoV-2, but some were.”

Dr. Ko framed her remarks largely on a case collection survey of images and clinical data from 375 patients in Spain with suspected or confirmed COVID-19 that was published online April 29, 2020, in the British Journal of Dermatology (doi: 10.1111/bjd.19163). Cutaneous manifestations included early vesicular eruptions mainly on the trunk or limbs (9%), maculopapular (47%) to urticarial lesions (19%) mainly on the trunk, and acral areas of erythema sometimes with vesicles or erosion (perniosis-like) (19%) that seemed to be a later manifestation of COVID-19. Retiform purpura or necrosis (6%) was most concerning in terms of skin disease, with an associated with a mortality of 10%.

On histology, the early vesicular eruptions are typically marked by dyskeratotic keratinocytes, Dr. Ko said, while urticarial lesions are characterized by a mixed dermal infiltrate; maculopapular lesions were a broad category. “There are some case reports that show spongiotic dermatitis or parakeratosis with a lymphocytic infiltrate,” she said. “A caveat to keep in mind is that, although these patients may definitely have COVID-19 and be confirmed to have it by testing, hypersensitivity reactions may be due to the multiple medications they’re on.”

Patients can develop a spectrum of lesions that are suggestive of vascular damage or occlusion, Dr. Ko continued. Livedoid lesions may remain static and not eventuate into necrosis or purpura but will self-resolve. Purpuric lesions and acral gangrene have been described, and these lesions correspond to vascular occlusion on biopsy.

A later manifestation are the so-called “COVID toes” with a superficial and deep lymphocytic infiltrate, as published June 1, 2020, in JAAD Case Reports: (doi: 10.1016/j.jdcr.2020.04.011).

“There are patients in the literature that have slightly different pathology, with lymphocytic inflammation as well as occlusion of vessels,” Dr. Ko said. A paper published June 20, 2020, in the British Journal of Dermatology used immunohistochemical staining against the SARS-CoV-2 spike protein, and biopsies of “COVID toes” had positive staining of endothelial cells, supporting the notion that “COVID toes” are a direct manifestation of viral infection (doi: 10.1111/bjd.19327).

“There’s a lot that we still don’t know, and some patterns are going to be outliers,” Dr. Ko concluded. “[As for] determining which skin manifestations are directly from coronavirus infection within the skin, more study is needed and likely time will tell.” She reported having no financial disclosures relevant to her talk.

dbrunk@mdedge.com

Acoustic subscision represents a novel, noninvasive treatment to improve the appearance of cellulite, results from a pivotal multicenter study demonstrated.

After a single treatment, it provided a roughly 1.16 point reduction in the five-point Cellulite Severity Scale at 12 weeks, which corresponds to a roughly 32.5% reduction in cellulite.

“In cellulite, we know that the septa within the fat – those fibrous bands that pull down the skin and tether – lead to the traditional look of cellulite dimples and ridges,” lead study author Elizabeth Tanzi, MD, said during a late-breaking abstract session at the virtual annual meeting of the American Academy of Dermatology. A rapid acoustic pulse (RAP) device being developed by Soliton emits rapid acoustic pulses and shock waves at 50 Hz that are transmitted through the skin. The pulses “rupture and shear the fibrotic septa, which causes release of the septa and smoothing of the skin dimples,” explained Dr. Tanzi, director of Capital Laser & Skin Care in Chevy Chase, Md.

She added that the repetition rate of the RAP device makes it stand out from other technologies currently on the market for cellulite treatment. “The repetition rate and very short rise times provide microscopic mechanical destruction to the targeted cellular level structures and the vacuoles,” Dr. Tanzi said. “The high peak pressure and fast repetition rate exploit the viscoelastic nature of the tissue. It’s the rapid rate at which the energy is being delivered, as well as the very short times that energy is being delivered, that makes the technology an entirely different device-tissue interaction.”

The physical effects observed occur in the extracellular matrix and in the destruction of fibrous septa. “That’s the acoustic subcision,” she continued. “But also, there’s no cavitation and there are nonthermal physical effects. There is some investigational research going into what biologic effects those shock waves have on the rest of the tissue, looking into neocollagenesis, potential angiogenesis, potential lymphangiogenesis, as well as inflammation inhibition.”

In a prospective pivotal clinical trial conducted at four sites, Dr. Tanzi and her colleagues evaluated the safety and effectiveness of the RAP device in 62 female patients who were treated with a single, rapid acoustic pulse treatment comprised of 1-2 minutes on each identified dimple or large ridge of cellulite. This amounted to a 19- to 33-minute treatment session for each patient. No anesthesia was required, and photographs were taken on all sites with QuantifiCare medical imaging software.

“It’s completely noninvasive and it’s truly an incisionless treatment,” Dr. Tanzi said of the procedure. “The skin’s never punctured. There’s physician oversight, but it is highly delegatable, and there is no recovery time for the patient.”

Following treatment, adverse effects and tolerability were reported, and safety and efficacy were assessed at 12 weeks. Efficacy was determined by photographic assessment by three blinded independent physicians who used a validated, simplified version of the Cellulite Severity Scale (CSS), a 0-5 scale based on the number of cellulite depressions, as well as the average depth of those depressions.

The mean age of patients was 43 years, 92% were white, and their mean body mass index was 24.5 kg/m². The average time of treatment was 28 minutes. Based on the CSS scores, the researchers found that 87% of the study subjects had some improvement of their cellulite after a single RAP treatment. “If you break the data down further, half of patients had at least a 30% reduction of their CSS, and almost one-quarter had a 50% improvement of their CSS,” Dr. Tanzi said. “Overall, we saw a reduction of a 1.16 level on that six-point scale, which translates roughly into 32.5% reduction of the look of their cellulite from the baseline score.”

In addition, 84% of the time, the blinded assessors were able to correctly identify pre- and posttreatment unlabeled photos that they were presented at the 3-month mark. Those same blinded assessors graded about 86% of the treated cellulite areas as appearing either improved, much improved, or very much improved on the Global Aesthetic Improvement Scale (GAIS).

“We found a very favorable side-effect profile, although 95% of patients had some redness to their skin,” Dr. Tanzi added. “They had some erythema and folliculitis, but it was transient and very mild. In addition, 98% of patients said that the procedure was tolerable.”

As for pain, on a 0-10 scale, with 10 being the worst, subjects rated their pain level at 2.4 during the treatment and 0.3 immediately afterward. On subject satisfaction surveys, 92% of the patient said that they “agree” or “strongly agree” that their cellulite appeared improved.

“Patients with moderate cellulite seem to respond [to this treatment], too,” Dr. Tanzi said. “I don’t think there’s a ceiling or a floor to which we have to pigeonhole patients into potentially treating with this device. I think the key is [targeting] cellulite and not necessarily skin laxity.”

She emphasized that much remains to be known about the RAP device for treating cellulite. “What happens if we do multiple treatments to the tissue?” she asked. “Also, we need to further investigate what’s happening in the tissue, because not only does it seem like we’re getting a cleaving of the fibrous septa, but what is happening to the fibroblasts? What’s really happening in the tissue on a molecular level when those rapid acoustic pulses are going through the skin? There’s a lot of unanswered questions, but this is exciting technology.”

According to a news release from Soliton, the company is further reviewing and analyzing these results for inclusion in a marketing application to the Food and Drug Administration.

Soliton sponsored the trial. Dr. Tanzi disclosed that she is either a consultant for or is a member of the scientific advisory board for Allergan/Coolsculpting, Beiersdorf, Cutera, Merz/Ulthera, Pulse Biosciences, Sciton, Soliton, Solta, and Syneron/Candela.

dbrunk@mdedge.com

Acoustic subscision represents a novel, noninvasive treatment to improve the appearance of cellulite, results from a pivotal multicenter study demonstrated.

After a single treatment, it provided a roughly 1.16 point reduction in the five-point Cellulite Severity Scale at 12 weeks, which corresponds to a roughly 32.5% reduction in cellulite.

“In cellulite, we know that the septa within the fat – those fibrous bands that pull down the skin and tether – lead to the traditional look of cellulite dimples and ridges,” lead study author Elizabeth Tanzi, MD, said during a late-breaking abstract session at the virtual annual meeting of the American Academy of Dermatology. A rapid acoustic pulse (RAP) device being developed by Soliton emits rapid acoustic pulses and shock waves at 50 Hz that are transmitted through the skin. The pulses “rupture and shear the fibrotic septa, which causes release of the septa and smoothing of the skin dimples,” explained Dr. Tanzi, director of Capital Laser & Skin Care in Chevy Chase, Md.

She added that the repetition rate of the RAP device makes it stand out from other technologies currently on the market for cellulite treatment. “The repetition rate and very short rise times provide microscopic mechanical destruction to the targeted cellular level structures and the vacuoles,” Dr. Tanzi said. “The high peak pressure and fast repetition rate exploit the viscoelastic nature of the tissue. It’s the rapid rate at which the energy is being delivered, as well as the very short times that energy is being delivered, that makes the technology an entirely different device-tissue interaction.”

The physical effects observed occur in the extracellular matrix and in the destruction of fibrous septa. “That’s the acoustic subcision,” she continued. “But also, there’s no cavitation and there are nonthermal physical effects. There is some investigational research going into what biologic effects those shock waves have on the rest of the tissue, looking into neocollagenesis, potential angiogenesis, potential lymphangiogenesis, as well as inflammation inhibition.”

In a prospective pivotal clinical trial conducted at four sites, Dr. Tanzi and her colleagues evaluated the safety and effectiveness of the RAP device in 62 female patients who were treated with a single, rapid acoustic pulse treatment comprised of 1-2 minutes on each identified dimple or large ridge of cellulite. This amounted to a 19- to 33-minute treatment session for each patient. No anesthesia was required, and photographs were taken on all sites with QuantifiCare medical imaging software.

“It’s completely noninvasive and it’s truly an incisionless treatment,” Dr. Tanzi said of the procedure. “The skin’s never punctured. There’s physician oversight, but it is highly delegatable, and there is no recovery time for the patient.”

Following treatment, adverse effects and tolerability were reported, and safety and efficacy were assessed at 12 weeks. Efficacy was determined by photographic assessment by three blinded independent physicians who used a validated, simplified version of the Cellulite Severity Scale (CSS), a 0-5 scale based on the number of cellulite depressions, as well as the average depth of those depressions.

The mean age of patients was 43 years, 92% were white, and their mean body mass index was 24.5 kg/m². The average time of treatment was 28 minutes. Based on the CSS scores, the researchers found that 87% of the study subjects had some improvement of their cellulite after a single RAP treatment. “If you break the data down further, half of patients had at least a 30% reduction of their CSS, and almost one-quarter had a 50% improvement of their CSS,” Dr. Tanzi said. “Overall, we saw a reduction of a 1.16 level on that six-point scale, which translates roughly into 32.5% reduction of the look of their cellulite from the baseline score.”

In addition, 84% of the time, the blinded assessors were able to correctly identify pre- and posttreatment unlabeled photos that they were presented at the 3-month mark. Those same blinded assessors graded about 86% of the treated cellulite areas as appearing either improved, much improved, or very much improved on the Global Aesthetic Improvement Scale (GAIS).

“We found a very favorable side-effect profile, although 95% of patients had some redness to their skin,” Dr. Tanzi added. “They had some erythema and folliculitis, but it was transient and very mild. In addition, 98% of patients said that the procedure was tolerable.”

As for pain, on a 0-10 scale, with 10 being the worst, subjects rated their pain level at 2.4 during the treatment and 0.3 immediately afterward. On subject satisfaction surveys, 92% of the patient said that they “agree” or “strongly agree” that their cellulite appeared improved.

“Patients with moderate cellulite seem to respond [to this treatment], too,” Dr. Tanzi said. “I don’t think there’s a ceiling or a floor to which we have to pigeonhole patients into potentially treating with this device. I think the key is [targeting] cellulite and not necessarily skin laxity.”

She emphasized that much remains to be known about the RAP device for treating cellulite. “What happens if we do multiple treatments to the tissue?” she asked. “Also, we need to further investigate what’s happening in the tissue, because not only does it seem like we’re getting a cleaving of the fibrous septa, but what is happening to the fibroblasts? What’s really happening in the tissue on a molecular level when those rapid acoustic pulses are going through the skin? There’s a lot of unanswered questions, but this is exciting technology.”

According to a news release from Soliton, the company is further reviewing and analyzing these results for inclusion in a marketing application to the Food and Drug Administration.

Soliton sponsored the trial. Dr. Tanzi disclosed that she is either a consultant for or is a member of the scientific advisory board for Allergan/Coolsculpting, Beiersdorf, Cutera, Merz/Ulthera, Pulse Biosciences, Sciton, Soliton, Solta, and Syneron/Candela.

dbrunk@mdedge.com

Acoustic subscision represents a novel, noninvasive treatment to improve the appearance of cellulite, results from a pivotal multicenter study demonstrated.

After a single treatment, it provided a roughly 1.16 point reduction in the five-point Cellulite Severity Scale at 12 weeks, which corresponds to a roughly 32.5% reduction in cellulite.

“In cellulite, we know that the septa within the fat – those fibrous bands that pull down the skin and tether – lead to the traditional look of cellulite dimples and ridges,” lead study author Elizabeth Tanzi, MD, said during a late-breaking abstract session at the virtual annual meeting of the American Academy of Dermatology. A rapid acoustic pulse (RAP) device being developed by Soliton emits rapid acoustic pulses and shock waves at 50 Hz that are transmitted through the skin. The pulses “rupture and shear the fibrotic septa, which causes release of the septa and smoothing of the skin dimples,” explained Dr. Tanzi, director of Capital Laser & Skin Care in Chevy Chase, Md.

She added that the repetition rate of the RAP device makes it stand out from other technologies currently on the market for cellulite treatment. “The repetition rate and very short rise times provide microscopic mechanical destruction to the targeted cellular level structures and the vacuoles,” Dr. Tanzi said. “The high peak pressure and fast repetition rate exploit the viscoelastic nature of the tissue. It’s the rapid rate at which the energy is being delivered, as well as the very short times that energy is being delivered, that makes the technology an entirely different device-tissue interaction.”

The physical effects observed occur in the extracellular matrix and in the destruction of fibrous septa. “That’s the acoustic subcision,” she continued. “But also, there’s no cavitation and there are nonthermal physical effects. There is some investigational research going into what biologic effects those shock waves have on the rest of the tissue, looking into neocollagenesis, potential angiogenesis, potential lymphangiogenesis, as well as inflammation inhibition.”

In a prospective pivotal clinical trial conducted at four sites, Dr. Tanzi and her colleagues evaluated the safety and effectiveness of the RAP device in 62 female patients who were treated with a single, rapid acoustic pulse treatment comprised of 1-2 minutes on each identified dimple or large ridge of cellulite. This amounted to a 19- to 33-minute treatment session for each patient. No anesthesia was required, and photographs were taken on all sites with QuantifiCare medical imaging software.

“It’s completely noninvasive and it’s truly an incisionless treatment,” Dr. Tanzi said of the procedure. “The skin’s never punctured. There’s physician oversight, but it is highly delegatable, and there is no recovery time for the patient.”

Following treatment, adverse effects and tolerability were reported, and safety and efficacy were assessed at 12 weeks. Efficacy was determined by photographic assessment by three blinded independent physicians who used a validated, simplified version of the Cellulite Severity Scale (CSS), a 0-5 scale based on the number of cellulite depressions, as well as the average depth of those depressions.

The mean age of patients was 43 years, 92% were white, and their mean body mass index was 24.5 kg/m². The average time of treatment was 28 minutes. Based on the CSS scores, the researchers found that 87% of the study subjects had some improvement of their cellulite after a single RAP treatment. “If you break the data down further, half of patients had at least a 30% reduction of their CSS, and almost one-quarter had a 50% improvement of their CSS,” Dr. Tanzi said. “Overall, we saw a reduction of a 1.16 level on that six-point scale, which translates roughly into 32.5% reduction of the look of their cellulite from the baseline score.”

In addition, 84% of the time, the blinded assessors were able to correctly identify pre- and posttreatment unlabeled photos that they were presented at the 3-month mark. Those same blinded assessors graded about 86% of the treated cellulite areas as appearing either improved, much improved, or very much improved on the Global Aesthetic Improvement Scale (GAIS).

“We found a very favorable side-effect profile, although 95% of patients had some redness to their skin,” Dr. Tanzi added. “They had some erythema and folliculitis, but it was transient and very mild. In addition, 98% of patients said that the procedure was tolerable.”

As for pain, on a 0-10 scale, with 10 being the worst, subjects rated their pain level at 2.4 during the treatment and 0.3 immediately afterward. On subject satisfaction surveys, 92% of the patient said that they “agree” or “strongly agree” that their cellulite appeared improved.

“Patients with moderate cellulite seem to respond [to this treatment], too,” Dr. Tanzi said. “I don’t think there’s a ceiling or a floor to which we have to pigeonhole patients into potentially treating with this device. I think the key is [targeting] cellulite and not necessarily skin laxity.”

She emphasized that much remains to be known about the RAP device for treating cellulite. “What happens if we do multiple treatments to the tissue?” she asked. “Also, we need to further investigate what’s happening in the tissue, because not only does it seem like we’re getting a cleaving of the fibrous septa, but what is happening to the fibroblasts? What’s really happening in the tissue on a molecular level when those rapid acoustic pulses are going through the skin? There’s a lot of unanswered questions, but this is exciting technology.”

According to a news release from Soliton, the company is further reviewing and analyzing these results for inclusion in a marketing application to the Food and Drug Administration.

Soliton sponsored the trial. Dr. Tanzi disclosed that she is either a consultant for or is a member of the scientific advisory board for Allergan/Coolsculpting, Beiersdorf, Cutera, Merz/Ulthera, Pulse Biosciences, Sciton, Soliton, Solta, and Syneron/Candela.

dbrunk@mdedge.com

Use of statins or other lipid-lowering drugs was associated with a lower risk of dying from colorectal cancer in a large study, investigators reported.

Use of lipid-lowering medication was linked to a 56% lower risk of colorectal cancer death among individuals with no cancer at baseline who were enrolled in the Atherosclerosis Risk in Communities (ARIC) study. The reduction in mortality risk was evident regardless of sex, race, age, or how long patients had been on lipid-lowering drugs.

Michael T. Marrone, PhD, of Johns Hopkins University, Baltimore, and colleagues detailed these findings in a poster presented at the AACR virtual meeting II.

“Definitely for those individuals at average risk for colorectal cancer, if their primary care doctor recommends a lipid-lowering medication for cardiovascular disease prevention, they should follow their doctor’s advice,” Dr. Marrone said in an interview.

“We really can’t say that they should take this specifically for colon cancer prevention, but they should just follow the recommendation for cardiovascular disease prevention,” he added.

While previous studies have linked lipid-lowering drugs, and statins in particular, to a modestly reduced risk of developing colorectal cancer, the impact on risk by factors such as sex, race, and duration of use have not been well characterized, according to Dr. Marrone.

Another motivation for this study was to determine, in participants free of cancer at baseline, the risk of actually dying from this cancer. “That endpoint has not been well studied in the literature at all,” Dr. Marrone said.

To address those gaps, Dr. Marrone and colleagues analyzed data on 14,428 patients from the ARIC study who were cancer free at study visits between 1990 and 1992. Follow-up continued through the end of 2015 or until death, whichever came first.

A total of 384 incident colorectal cancer cases and 144 deaths were seen over 290,249 person-years at risk. The patients’ mean age was 57 years, 54.9% were women, and 27.9% were black. At scheduled follow-up visits from 1996 to 1998, 22% of patients were taking lipid-lowering drugs, mostly statins.

Compared with patients who never used lipid-lowering medications, patients who had ever used a lipid-lowering drug had a lower risk of colorectal cancer incidence (hazard ratio, 0.72). The incidence of colorectal cancer was lower among all lipid-lowering drug users, including men (HR, 0.69), women (HR, 0.76), black patients (HR, 0.60), and white patients (HR, 0.77).

Similarly, colorectal cancer–related death was lower among patients who had ever used a lipid-lowering drug (HR, 0.44). That association was apparent in men (HR, 0.58), women (HR, 0.33), black patients (HR, 0.63), and white patients (HR, 0.40).

In addition, the mortality risk was lower among lipid-lowering drug users regardless of duration of use or age at first use. The HR was 0.50 for patients taking lipid-lowering drugs for less than 15 years and 0.44 for patients taking the drugs for 15 years or more. HRs by age were 0.69 for patients aged 50-59 years, 0.45 for patients aged 60-69 years, and 0.57 for patients aged 70 and older.

While results of this particular study do help “move the needle forward” in terms of characterizing the relationship between lipid-lowering drugs and colorectal cancer risk, further studies are needed to better characterize the effects of long-term statin use, said Jennifer M. Weiss, MD, of the University of Wisconsin–Madison.

Clinical studies of the impact of statins on colorectal neoplasias have produced inconsistent results, Dr. Weiss and coauthor Bryson W. Katona, MD, PhD, wrote in a review article on chemoprevention in colorectal cancer.

“I definitely think there have been some studies that showed a modestly reduced risk,” Dr. Weiss said in an interview. “Unfortunately, there are also are some studies that show an increased risk of adenomas, and then there’s some studies that show no significant change. So we just can’t unequivocally confirm that there’s a significant association between statin use and decreased risk of developing colorectal cancer or adenomas.”

This research was funded by grants from the National Cancer Institute; the National Heart, Lung, and Blood Institute; the National Program of Cancer Registries; and the American Association for Cancer Research. Dr. Marrone disclosed no conflicts of interest. Dr. Weiss was an investigator for the CPP FAP-310 trial (NCT01483144) and received no salary support for her participation in the trial.

SOURCE: Marrone MT et al. AACR 2020, Abstract 2357.

Use of statins or other lipid-lowering drugs was associated with a lower risk of dying from colorectal cancer in a large study, investigators reported.

Use of lipid-lowering medication was linked to a 56% lower risk of colorectal cancer death among individuals with no cancer at baseline who were enrolled in the Atherosclerosis Risk in Communities (ARIC) study. The reduction in mortality risk was evident regardless of sex, race, age, or how long patients had been on lipid-lowering drugs.

Michael T. Marrone, PhD, of Johns Hopkins University, Baltimore, and colleagues detailed these findings in a poster presented at the AACR virtual meeting II.

“Definitely for those individuals at average risk for colorectal cancer, if their primary care doctor recommends a lipid-lowering medication for cardiovascular disease prevention, they should follow their doctor’s advice,” Dr. Marrone said in an interview.

“We really can’t say that they should take this specifically for colon cancer prevention, but they should just follow the recommendation for cardiovascular disease prevention,” he added.

While previous studies have linked lipid-lowering drugs, and statins in particular, to a modestly reduced risk of developing colorectal cancer, the impact on risk by factors such as sex, race, and duration of use have not been well characterized, according to Dr. Marrone.

Another motivation for this study was to determine, in participants free of cancer at baseline, the risk of actually dying from this cancer. “That endpoint has not been well studied in the literature at all,” Dr. Marrone said.

To address those gaps, Dr. Marrone and colleagues analyzed data on 14,428 patients from the ARIC study who were cancer free at study visits between 1990 and 1992. Follow-up continued through the end of 2015 or until death, whichever came first.

A total of 384 incident colorectal cancer cases and 144 deaths were seen over 290,249 person-years at risk. The patients’ mean age was 57 years, 54.9% were women, and 27.9% were black. At scheduled follow-up visits from 1996 to 1998, 22% of patients were taking lipid-lowering drugs, mostly statins.

Compared with patients who never used lipid-lowering medications, patients who had ever used a lipid-lowering drug had a lower risk of colorectal cancer incidence (hazard ratio, 0.72). The incidence of colorectal cancer was lower among all lipid-lowering drug users, including men (HR, 0.69), women (HR, 0.76), black patients (HR, 0.60), and white patients (HR, 0.77).

Similarly, colorectal cancer–related death was lower among patients who had ever used a lipid-lowering drug (HR, 0.44). That association was apparent in men (HR, 0.58), women (HR, 0.33), black patients (HR, 0.63), and white patients (HR, 0.40).

In addition, the mortality risk was lower among lipid-lowering drug users regardless of duration of use or age at first use. The HR was 0.50 for patients taking lipid-lowering drugs for less than 15 years and 0.44 for patients taking the drugs for 15 years or more. HRs by age were 0.69 for patients aged 50-59 years, 0.45 for patients aged 60-69 years, and 0.57 for patients aged 70 and older.

While results of this particular study do help “move the needle forward” in terms of characterizing the relationship between lipid-lowering drugs and colorectal cancer risk, further studies are needed to better characterize the effects of long-term statin use, said Jennifer M. Weiss, MD, of the University of Wisconsin–Madison.

Clinical studies of the impact of statins on colorectal neoplasias have produced inconsistent results, Dr. Weiss and coauthor Bryson W. Katona, MD, PhD, wrote in a review article on chemoprevention in colorectal cancer.

“I definitely think there have been some studies that showed a modestly reduced risk,” Dr. Weiss said in an interview. “Unfortunately, there are also are some studies that show an increased risk of adenomas, and then there’s some studies that show no significant change. So we just can’t unequivocally confirm that there’s a significant association between statin use and decreased risk of developing colorectal cancer or adenomas.”

This research was funded by grants from the National Cancer Institute; the National Heart, Lung, and Blood Institute; the National Program of Cancer Registries; and the American Association for Cancer Research. Dr. Marrone disclosed no conflicts of interest. Dr. Weiss was an investigator for the CPP FAP-310 trial (NCT01483144) and received no salary support for her participation in the trial.

SOURCE: Marrone MT et al. AACR 2020, Abstract 2357.

Use of statins or other lipid-lowering drugs was associated with a lower risk of dying from colorectal cancer in a large study, investigators reported.

Use of lipid-lowering medication was linked to a 56% lower risk of colorectal cancer death among individuals with no cancer at baseline who were enrolled in the Atherosclerosis Risk in Communities (ARIC) study. The reduction in mortality risk was evident regardless of sex, race, age, or how long patients had been on lipid-lowering drugs.

Michael T. Marrone, PhD, of Johns Hopkins University, Baltimore, and colleagues detailed these findings in a poster presented at the AACR virtual meeting II.

“Definitely for those individuals at average risk for colorectal cancer, if their primary care doctor recommends a lipid-lowering medication for cardiovascular disease prevention, they should follow their doctor’s advice,” Dr. Marrone said in an interview.

“We really can’t say that they should take this specifically for colon cancer prevention, but they should just follow the recommendation for cardiovascular disease prevention,” he added.

While previous studies have linked lipid-lowering drugs, and statins in particular, to a modestly reduced risk of developing colorectal cancer, the impact on risk by factors such as sex, race, and duration of use have not been well characterized, according to Dr. Marrone.

Another motivation for this study was to determine, in participants free of cancer at baseline, the risk of actually dying from this cancer. “That endpoint has not been well studied in the literature at all,” Dr. Marrone said.

To address those gaps, Dr. Marrone and colleagues analyzed data on 14,428 patients from the ARIC study who were cancer free at study visits between 1990 and 1992. Follow-up continued through the end of 2015 or until death, whichever came first.

A total of 384 incident colorectal cancer cases and 144 deaths were seen over 290,249 person-years at risk. The patients’ mean age was 57 years, 54.9% were women, and 27.9% were black. At scheduled follow-up visits from 1996 to 1998, 22% of patients were taking lipid-lowering drugs, mostly statins.

Compared with patients who never used lipid-lowering medications, patients who had ever used a lipid-lowering drug had a lower risk of colorectal cancer incidence (hazard ratio, 0.72). The incidence of colorectal cancer was lower among all lipid-lowering drug users, including men (HR, 0.69), women (HR, 0.76), black patients (HR, 0.60), and white patients (HR, 0.77).

Similarly, colorectal cancer–related death was lower among patients who had ever used a lipid-lowering drug (HR, 0.44). That association was apparent in men (HR, 0.58), women (HR, 0.33), black patients (HR, 0.63), and white patients (HR, 0.40).

In addition, the mortality risk was lower among lipid-lowering drug users regardless of duration of use or age at first use. The HR was 0.50 for patients taking lipid-lowering drugs for less than 15 years and 0.44 for patients taking the drugs for 15 years or more. HRs by age were 0.69 for patients aged 50-59 years, 0.45 for patients aged 60-69 years, and 0.57 for patients aged 70 and older.

While results of this particular study do help “move the needle forward” in terms of characterizing the relationship between lipid-lowering drugs and colorectal cancer risk, further studies are needed to better characterize the effects of long-term statin use, said Jennifer M. Weiss, MD, of the University of Wisconsin–Madison.

Clinical studies of the impact of statins on colorectal neoplasias have produced inconsistent results, Dr. Weiss and coauthor Bryson W. Katona, MD, PhD, wrote in a review article on chemoprevention in colorectal cancer.

“I definitely think there have been some studies that showed a modestly reduced risk,” Dr. Weiss said in an interview. “Unfortunately, there are also are some studies that show an increased risk of adenomas, and then there’s some studies that show no significant change. So we just can’t unequivocally confirm that there’s a significant association between statin use and decreased risk of developing colorectal cancer or adenomas.”

This research was funded by grants from the National Cancer Institute; the National Heart, Lung, and Blood Institute; the National Program of Cancer Registries; and the American Association for Cancer Research. Dr. Marrone disclosed no conflicts of interest. Dr. Weiss was an investigator for the CPP FAP-310 trial (NCT01483144) and received no salary support for her participation in the trial.

SOURCE: Marrone MT et al. AACR 2020, Abstract 2357.

Older adults, particularly postmenopausal women, are often advised to pursue low-impact, low-intensity exercise as a way to preserve joint health, but that approach might actually contribute to a decline in bone mineral density, researchers report.

Concerns about falls and fracture risk have led many clinicians to advise against higher-impact activities, like jumping, but that is exactly the type of activity that improves bone density and physical function, said Belinda Beck, PhD, professor at the Griffith University School of Allied Health Sciences in Southport, Australia.

“There has always been a quandary in terms of pursuing research on this,” she said in an interview. “We know from animal studies that bone only responds to high-intensity activity, but we worry about advising that for people with low bone mass, so instead we give them medications.”

“But not everyone likes to go on meds, they’re not 100% effective, and they’re not free of side effects,” said Beck, who is also the owner and director of The Bone Clinic in Brisbane, Australia.

In 2014, to assess whether high-intensity resistance and impact training (HiRIT) was a safe and effective way to improve bone mass, Beck and her colleagues conducted the LIFTMOR study of 101 postmenopausal women. The researchers showed that bone mineral density in the lumbar spine and femoral neck regions and functional performance measures were significantly better in the 49 participants randomized to HiRIT for 8 months than in the 52 randomized to low-intensity training.

Three years after the completion of LIFTMOR, the researchers looked at bone mineral density in 23 women from the HiRIT group in their retrospective observational study, the results of which were presented at the virtual American College of Sports Medicine 2020 Annual Meeting.

Ongoing gains were significantly better for the seven participants who continued with HiRIT (at least 25% compliance) than for the 16 who did not when looking at both bone mineral density of the lumbar spine (8.63% vs. 2.18%; P = .042) and femoral neck (3.67% vs. 2.85%; P = 0.14).

However, the women who discontinued HiRIT after 8 months maintained the gains in bone mineral density that they had achieved 3 years earlier.

Functional outcomes in the women who continued HiRIT were better than those in the women who did not, but the differences were not significant.

“The takeaway here is that this type of exercise appears to be a highly effective therapy to reduce risk of osteoporotic fracture, since it improves bone mass,” Beck said.

Jump more, lose less bone density

Given the widespread reluctance to suggest HiRIT-type activity to those with low bone mass, this research is significant, said Vanessa Yingling, PhD, from the Department of Kinesiology at California State University, East Bay.

“Once women hit 60, they’re somehow regarded as frail, but that becomes a self-fulfilling prophecy when we take this kinder, gentler approach to exercise,” Yingling said in an interview. “Building bone density in older adults is important, but maintaining current bone density is just as crucial. Without high-impact activity, we are likely to see decelerating density at a faster rate.”

The other key to the recent research is the functional testing, Yingling added. In addition to bone density measures, high-intensity activity can improve mobility and muscle strength, as the study noted.

This type of activity can be done in shorter bursts, making these workouts more efficient, she explained. For example, a Tabata high-intensity interval training session usually takes about 10 minutes, warm-up and cool-down included.

“A HiRIT workout even once or twice a week would likely improve function, strength, and bone density maintenance,” Beck said. “The result of that would be better fall prevention and potentially less medication usage for BMD issues.”

Both men and women can benefit from a HiRIT workout, Beck and Yingling said. Initially, supervision by a knowledgeable trainer or physical therapist is ideal, they added.

This article first appeared on Medscape.com.

Older adults, particularly postmenopausal women, are often advised to pursue low-impact, low-intensity exercise as a way to preserve joint health, but that approach might actually contribute to a decline in bone mineral density, researchers report.

Concerns about falls and fracture risk have led many clinicians to advise against higher-impact activities, like jumping, but that is exactly the type of activity that improves bone density and physical function, said Belinda Beck, PhD, professor at the Griffith University School of Allied Health Sciences in Southport, Australia.

“There has always been a quandary in terms of pursuing research on this,” she said in an interview. “We know from animal studies that bone only responds to high-intensity activity, but we worry about advising that for people with low bone mass, so instead we give them medications.”

“But not everyone likes to go on meds, they’re not 100% effective, and they’re not free of side effects,” said Beck, who is also the owner and director of The Bone Clinic in Brisbane, Australia.

In 2014, to assess whether high-intensity resistance and impact training (HiRIT) was a safe and effective way to improve bone mass, Beck and her colleagues conducted the LIFTMOR study of 101 postmenopausal women. The researchers showed that bone mineral density in the lumbar spine and femoral neck regions and functional performance measures were significantly better in the 49 participants randomized to HiRIT for 8 months than in the 52 randomized to low-intensity training.

Three years after the completion of LIFTMOR, the researchers looked at bone mineral density in 23 women from the HiRIT group in their retrospective observational study, the results of which were presented at the virtual American College of Sports Medicine 2020 Annual Meeting.

Ongoing gains were significantly better for the seven participants who continued with HiRIT (at least 25% compliance) than for the 16 who did not when looking at both bone mineral density of the lumbar spine (8.63% vs. 2.18%; P = .042) and femoral neck (3.67% vs. 2.85%; P = 0.14).

However, the women who discontinued HiRIT after 8 months maintained the gains in bone mineral density that they had achieved 3 years earlier.

Functional outcomes in the women who continued HiRIT were better than those in the women who did not, but the differences were not significant.

“The takeaway here is that this type of exercise appears to be a highly effective therapy to reduce risk of osteoporotic fracture, since it improves bone mass,” Beck said.

Jump more, lose less bone density

Given the widespread reluctance to suggest HiRIT-type activity to those with low bone mass, this research is significant, said Vanessa Yingling, PhD, from the Department of Kinesiology at California State University, East Bay.

“Once women hit 60, they’re somehow regarded as frail, but that becomes a self-fulfilling prophecy when we take this kinder, gentler approach to exercise,” Yingling said in an interview. “Building bone density in older adults is important, but maintaining current bone density is just as crucial. Without high-impact activity, we are likely to see decelerating density at a faster rate.”

The other key to the recent research is the functional testing, Yingling added. In addition to bone density measures, high-intensity activity can improve mobility and muscle strength, as the study noted.

This type of activity can be done in shorter bursts, making these workouts more efficient, she explained. For example, a Tabata high-intensity interval training session usually takes about 10 minutes, warm-up and cool-down included.

“A HiRIT workout even once or twice a week would likely improve function, strength, and bone density maintenance,” Beck said. “The result of that would be better fall prevention and potentially less medication usage for BMD issues.”

Both men and women can benefit from a HiRIT workout, Beck and Yingling said. Initially, supervision by a knowledgeable trainer or physical therapist is ideal, they added.

This article first appeared on Medscape.com.

Older adults, particularly postmenopausal women, are often advised to pursue low-impact, low-intensity exercise as a way to preserve joint health, but that approach might actually contribute to a decline in bone mineral density, researchers report.

Concerns about falls and fracture risk have led many clinicians to advise against higher-impact activities, like jumping, but that is exactly the type of activity that improves bone density and physical function, said Belinda Beck, PhD, professor at the Griffith University School of Allied Health Sciences in Southport, Australia.

“There has always been a quandary in terms of pursuing research on this,” she said in an interview. “We know from animal studies that bone only responds to high-intensity activity, but we worry about advising that for people with low bone mass, so instead we give them medications.”

“But not everyone likes to go on meds, they’re not 100% effective, and they’re not free of side effects,” said Beck, who is also the owner and director of The Bone Clinic in Brisbane, Australia.

In 2014, to assess whether high-intensity resistance and impact training (HiRIT) was a safe and effective way to improve bone mass, Beck and her colleagues conducted the LIFTMOR study of 101 postmenopausal women. The researchers showed that bone mineral density in the lumbar spine and femoral neck regions and functional performance measures were significantly better in the 49 participants randomized to HiRIT for 8 months than in the 52 randomized to low-intensity training.

Three years after the completion of LIFTMOR, the researchers looked at bone mineral density in 23 women from the HiRIT group in their retrospective observational study, the results of which were presented at the virtual American College of Sports Medicine 2020 Annual Meeting.

Ongoing gains were significantly better for the seven participants who continued with HiRIT (at least 25% compliance) than for the 16 who did not when looking at both bone mineral density of the lumbar spine (8.63% vs. 2.18%; P = .042) and femoral neck (3.67% vs. 2.85%; P = 0.14).

However, the women who discontinued HiRIT after 8 months maintained the gains in bone mineral density that they had achieved 3 years earlier.

Functional outcomes in the women who continued HiRIT were better than those in the women who did not, but the differences were not significant.

“The takeaway here is that this type of exercise appears to be a highly effective therapy to reduce risk of osteoporotic fracture, since it improves bone mass,” Beck said.

Jump more, lose less bone density

Given the widespread reluctance to suggest HiRIT-type activity to those with low bone mass, this research is significant, said Vanessa Yingling, PhD, from the Department of Kinesiology at California State University, East Bay.

“Once women hit 60, they’re somehow regarded as frail, but that becomes a self-fulfilling prophecy when we take this kinder, gentler approach to exercise,” Yingling said in an interview. “Building bone density in older adults is important, but maintaining current bone density is just as crucial. Without high-impact activity, we are likely to see decelerating density at a faster rate.”

The other key to the recent research is the functional testing, Yingling added. In addition to bone density measures, high-intensity activity can improve mobility and muscle strength, as the study noted.

This type of activity can be done in shorter bursts, making these workouts more efficient, she explained. For example, a Tabata high-intensity interval training session usually takes about 10 minutes, warm-up and cool-down included.

“A HiRIT workout even once or twice a week would likely improve function, strength, and bone density maintenance,” Beck said. “The result of that would be better fall prevention and potentially less medication usage for BMD issues.”

Both men and women can benefit from a HiRIT workout, Beck and Yingling said. Initially, supervision by a knowledgeable trainer or physical therapist is ideal, they added.

This article first appeared on Medscape.com.

A striking clinical feature of illness from SARS-CoV-2 is a marked increase in thrombotic and microvascular complications, or COVID-19–associated coagulopathy (CAC).

A new study suggests endothelial cell injury plays a major role in the pathogenesis of CAC, and blood levels of soluble thrombomodulin correlate with mortality.

George Goshua, MD, of Yale University, New Haven, Conn., presented this study as a late-breaking abstract at the virtual annual congress of the European Hematology Association.

Dr. Goshua cited past research showing CAC to be highly prevalent among hospitalized patients. Venous thromboembolism was found in 17% to 69% of patients, despite thromboprophylaxis.^1-4 Arterial thrombosis has been seen in 3.6% to 4.0% of patients,^1-3 and autopsy findings have shown microvascular thrombosis in as many as 87% of patients.^5-7

For their study, Dr. Goshua and colleagues assessed endothelial cell damage, platelet activation, and hemostatic and fibrinolytic cascade effects of CAC.

The investigators measured markers of endothelial cell injury and platelet activation, plasminogen activation inhibitor 1 (PAI-1), and coagulation factors in stable and critically ill patients hospitalized with COVID-19. In addition, the team sought to identify biomarkers of mortality in hospitalized patients.

Dr. Goshua and colleagues studied 68 adults hospitalized for suspected COVID-19 – 48 in the ICU and 20 outside the ICU. Patients in the ICU received mechanical ventilation, while the non-ICU patients required supplemental oxygen (≤3 L/min per nasal cannula).

There were more men than women (69% vs. 31%) in the ICU population but not in the non-ICU population (40% vs. 60%). There were no statistically significant differences in age or comorbid conditions between the ICU and non-ICU patients.
 

Results and interpretation

Consistent with augmentation of the coagulation cascade – and as expected – D-dimer and thrombin-antithrombin levels were high in both the ICU and non-ICU populations, but levels were significantly higher (P < .001) among the ICU patients.

Endogenous anticoagulants (antithrombin and proteins C and S) and fibrinolytic enzymes (alpha 2-antiplasmin) were preserved, verifying that CAC is distinct from disseminated intravascular coagulation. Classic fibrinolysis did not occur, as PAI-1 was high in ICU and non-ICU patients, and lysis-30 was normal in nearly all ICU patients (96%).

Von Willebrand factor antigen and activity levels and factor VIII levels were markedly elevated in non-ICU and ICU patients, but they were significantly higher (P < .001) in the ICU cohort. This supports the hypothesis that endothelial cell damage and platelet activation play major roles in CAC.

Similarly, soluble P-selectin, which is shed from endothelial cells and platelets, was dramatically elevated in ICU patients in comparison with controls and non-ICU patients (P < .001 for both comparisons).

Levels of soluble thrombomodulin, which is released from endothelial cells, were not significantly different in ICU patients and controls. However, given thrombomodulin’s significant role in the coagulation cascade, Dr. Goshua and colleagues plotted receiver operating curves to see if soluble thrombomodulin levels were predictive of mortality.

The results showed that soluble thrombomodulin correlated with the probability of survival, both overall and in ICU patients. Soluble thrombomodulin levels greater than 3.26 ng/mL were associated with significantly worse survival in all patients (P = .0087) and ICU patients (P = .0309).
 

Influence on therapy

Laboratory perturbations were detected in both ICU and non-ICU patients, and otherwise healthy outpatients have exhibited potentially life-threatening CAC, according to Dr. Goshua.

These findings suggest the prothrombotic state occurs early in the pathogenesis of SARS-CoV-2 infection, is driven by platelet activation and endotheliopathy, and becomes more pronounced with worsening severity of infection.

The results of this study prompted a change in how Yale–New Haven Hospital manages COVID-19 patients. Patients without a clinical contraindication now receive aspirin at 81 mg daily in addition to the anticoagulation regimen typically used for all hospitalized COVID-19 patients.

Investigations regarding other medications that can influence platelet-endothelial cell interactions and modulate endothelial cell damage in CAC – such as dipyridamole, defibrotide, and eculizumab – are planned.
 

Challenges and unanswered questions

Virchow’s triad was described by the eminent German physician, Rudolf Virchow, MD, in the 19th century. It refers to the three broad categories of factors that can predispose patients to thrombosis — circulatory stasis, hypercoagulability, and endothelial injury.

Although all of these elements could be operative in CAC, the current study suggests platelet activation and endothelial cell injury in CAC may be of primary importance.

Because of the limited ability to test critically ill patients and concerns regarding exposure of additional hospital personnel to COVID-19 patients, the current report lacked clarity about the relationship of the detected laboratory abnormalities to confirmed thrombotic events.

It is unknown whether endothelial cells in different organs are damaged uniformly. It is also unclear if the laboratory abnormalities identified in this analysis can be used to monitor response to therapy, to guide follow-up management of discharged patients with CAC, or to identify infected outpatients who should receive prophylactic anticoagulation.

The mechanism by which SARS-CoV-2 injures endothelial cells is not explained by these data. Neutrophil defensins and other prothrombotic peptides or markers of inflammation could play key roles in pathogenesis, assessment of disease severity, or monitoring for therapeutic efficacy.

Today, we have more sophisticated diagnostic tools than Dr. Virchow had. We also have the ability to record and rapidly disseminate information globally. Still, with regard to the COVID-19 pandemic, clinicians face many of the same challenges that confronted Dr. Virchow in his era.

The analysis conducted by Dr. Goshua and colleagues goes a long way toward elucidating some of the mechanisms and therapeutic targets to meet these challenges.

Dr. Goshua disclosed no conflicts of interest.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

SOURCE: Goshua G et al. EHA Congress. Abstract LB2605.

References

1. Klok FA et al. Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: An updated analysis. Thromb Res. 2020;191:148-50. doi: 10.1016/j.thromres.2020.04.041.

2. Thomas W et al. Thrombotic complications of patients admitted to intensive care with COVID-19 at a teaching hospital in the United Kingdom. Thromb Res. 2020;191:76-7. doi: 10.1016/j.thromres.2020.04.028

3. Lodigiani C et al. Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy. Thromb Res. 2020;191:9-14. doi: 10.1016/j.thromres.2020.04.024

4. Llitjos JF et al. High incidence of venous thromboembolic events in anticoagulated severe COVID-19 patients [published online ahead of print, 2020 Apr 22]. J Thromb Haemost. 2020;10.1111/jth.14869. doi: 10.1111/jth.14869

5. Carsana L et al. Pulmonary post-mortem findings in a large series of COVID-19 cases from Northern Italy. medRxiv 2020.04.19.20054262; doi: 10.1101/2020.04.19.20054262v1.

6. Menter T et al. Post-mortem examination of COVID19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings of lungs and other organs suggesting vascular dysfunction [published online ahead of print, 2020 May 4]. Histopathology. 2020;10.1111/his.14134. doi: 10.1111/his.14134

7. Lax SF, et al. Pulmonary arterial thrombosis in COVID-19 with fatal outcome: Results from a prospective, single-center, clinicopathologic case series [published online ahead of print, 2020 May 14]. Ann Intern Med. 2020;M20-2566. doi: 10.7326/M20-2566.

A striking clinical feature of illness from SARS-CoV-2 is a marked increase in thrombotic and microvascular complications, or COVID-19–associated coagulopathy (CAC).

A new study suggests endothelial cell injury plays a major role in the pathogenesis of CAC, and blood levels of soluble thrombomodulin correlate with mortality.

George Goshua, MD, of Yale University, New Haven, Conn., presented this study as a late-breaking abstract at the virtual annual congress of the European Hematology Association.

Dr. Goshua cited past research showing CAC to be highly prevalent among hospitalized patients. Venous thromboembolism was found in 17% to 69% of patients, despite thromboprophylaxis.^1-4 Arterial thrombosis has been seen in 3.6% to 4.0% of patients,^1-3 and autopsy findings have shown microvascular thrombosis in as many as 87% of patients.^5-7

For their study, Dr. Goshua and colleagues assessed endothelial cell damage, platelet activation, and hemostatic and fibrinolytic cascade effects of CAC.

The investigators measured markers of endothelial cell injury and platelet activation, plasminogen activation inhibitor 1 (PAI-1), and coagulation factors in stable and critically ill patients hospitalized with COVID-19. In addition, the team sought to identify biomarkers of mortality in hospitalized patients.

Dr. Goshua and colleagues studied 68 adults hospitalized for suspected COVID-19 – 48 in the ICU and 20 outside the ICU. Patients in the ICU received mechanical ventilation, while the non-ICU patients required supplemental oxygen (≤3 L/min per nasal cannula).

There were more men than women (69% vs. 31%) in the ICU population but not in the non-ICU population (40% vs. 60%). There were no statistically significant differences in age or comorbid conditions between the ICU and non-ICU patients.
 

Results and interpretation

Consistent with augmentation of the coagulation cascade – and as expected – D-dimer and thrombin-antithrombin levels were high in both the ICU and non-ICU populations, but levels were significantly higher (P < .001) among the ICU patients.

Endogenous anticoagulants (antithrombin and proteins C and S) and fibrinolytic enzymes (alpha 2-antiplasmin) were preserved, verifying that CAC is distinct from disseminated intravascular coagulation. Classic fibrinolysis did not occur, as PAI-1 was high in ICU and non-ICU patients, and lysis-30 was normal in nearly all ICU patients (96%).

Von Willebrand factor antigen and activity levels and factor VIII levels were markedly elevated in non-ICU and ICU patients, but they were significantly higher (P < .001) in the ICU cohort. This supports the hypothesis that endothelial cell damage and platelet activation play major roles in CAC.

Similarly, soluble P-selectin, which is shed from endothelial cells and platelets, was dramatically elevated in ICU patients in comparison with controls and non-ICU patients (P < .001 for both comparisons).

Levels of soluble thrombomodulin, which is released from endothelial cells, were not significantly different in ICU patients and controls. However, given thrombomodulin’s significant role in the coagulation cascade, Dr. Goshua and colleagues plotted receiver operating curves to see if soluble thrombomodulin levels were predictive of mortality.

The results showed that soluble thrombomodulin correlated with the probability of survival, both overall and in ICU patients. Soluble thrombomodulin levels greater than 3.26 ng/mL were associated with significantly worse survival in all patients (P = .0087) and ICU patients (P = .0309).
 

Influence on therapy

Laboratory perturbations were detected in both ICU and non-ICU patients, and otherwise healthy outpatients have exhibited potentially life-threatening CAC, according to Dr. Goshua.

These findings suggest the prothrombotic state occurs early in the pathogenesis of SARS-CoV-2 infection, is driven by platelet activation and endotheliopathy, and becomes more pronounced with worsening severity of infection.

The results of this study prompted a change in how Yale–New Haven Hospital manages COVID-19 patients. Patients without a clinical contraindication now receive aspirin at 81 mg daily in addition to the anticoagulation regimen typically used for all hospitalized COVID-19 patients.

Investigations regarding other medications that can influence platelet-endothelial cell interactions and modulate endothelial cell damage in CAC – such as dipyridamole, defibrotide, and eculizumab – are planned.
 

Challenges and unanswered questions

Virchow’s triad was described by the eminent German physician, Rudolf Virchow, MD, in the 19th century. It refers to the three broad categories of factors that can predispose patients to thrombosis — circulatory stasis, hypercoagulability, and endothelial injury.

Although all of these elements could be operative in CAC, the current study suggests platelet activation and endothelial cell injury in CAC may be of primary importance.

Because of the limited ability to test critically ill patients and concerns regarding exposure of additional hospital personnel to COVID-19 patients, the current report lacked clarity about the relationship of the detected laboratory abnormalities to confirmed thrombotic events.

It is unknown whether endothelial cells in different organs are damaged uniformly. It is also unclear if the laboratory abnormalities identified in this analysis can be used to monitor response to therapy, to guide follow-up management of discharged patients with CAC, or to identify infected outpatients who should receive prophylactic anticoagulation.

The mechanism by which SARS-CoV-2 injures endothelial cells is not explained by these data. Neutrophil defensins and other prothrombotic peptides or markers of inflammation could play key roles in pathogenesis, assessment of disease severity, or monitoring for therapeutic efficacy.

Today, we have more sophisticated diagnostic tools than Dr. Virchow had. We also have the ability to record and rapidly disseminate information globally. Still, with regard to the COVID-19 pandemic, clinicians face many of the same challenges that confronted Dr. Virchow in his era.

The analysis conducted by Dr. Goshua and colleagues goes a long way toward elucidating some of the mechanisms and therapeutic targets to meet these challenges.

Dr. Goshua disclosed no conflicts of interest.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

SOURCE: Goshua G et al. EHA Congress. Abstract LB2605.

References

1. Klok FA et al. Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: An updated analysis. Thromb Res. 2020;191:148-50. doi: 10.1016/j.thromres.2020.04.041.

2. Thomas W et al. Thrombotic complications of patients admitted to intensive care with COVID-19 at a teaching hospital in the United Kingdom. Thromb Res. 2020;191:76-7. doi: 10.1016/j.thromres.2020.04.028

3. Lodigiani C et al. Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy. Thromb Res. 2020;191:9-14. doi: 10.1016/j.thromres.2020.04.024

4. Llitjos JF et al. High incidence of venous thromboembolic events in anticoagulated severe COVID-19 patients [published online ahead of print, 2020 Apr 22]. J Thromb Haemost. 2020;10.1111/jth.14869. doi: 10.1111/jth.14869

5. Carsana L et al. Pulmonary post-mortem findings in a large series of COVID-19 cases from Northern Italy. medRxiv 2020.04.19.20054262; doi: 10.1101/2020.04.19.20054262v1.

6. Menter T et al. Post-mortem examination of COVID19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings of lungs and other organs suggesting vascular dysfunction [published online ahead of print, 2020 May 4]. Histopathology. 2020;10.1111/his.14134. doi: 10.1111/his.14134

7. Lax SF, et al. Pulmonary arterial thrombosis in COVID-19 with fatal outcome: Results from a prospective, single-center, clinicopathologic case series [published online ahead of print, 2020 May 14]. Ann Intern Med. 2020;M20-2566. doi: 10.7326/M20-2566.

A striking clinical feature of illness from SARS-CoV-2 is a marked increase in thrombotic and microvascular complications, or COVID-19–associated coagulopathy (CAC).

A new study suggests endothelial cell injury plays a major role in the pathogenesis of CAC, and blood levels of soluble thrombomodulin correlate with mortality.

George Goshua, MD, of Yale University, New Haven, Conn., presented this study as a late-breaking abstract at the virtual annual congress of the European Hematology Association.

Dr. Goshua cited past research showing CAC to be highly prevalent among hospitalized patients. Venous thromboembolism was found in 17% to 69% of patients, despite thromboprophylaxis.^1-4 Arterial thrombosis has been seen in 3.6% to 4.0% of patients,^1-3 and autopsy findings have shown microvascular thrombosis in as many as 87% of patients.^5-7

For their study, Dr. Goshua and colleagues assessed endothelial cell damage, platelet activation, and hemostatic and fibrinolytic cascade effects of CAC.

The investigators measured markers of endothelial cell injury and platelet activation, plasminogen activation inhibitor 1 (PAI-1), and coagulation factors in stable and critically ill patients hospitalized with COVID-19. In addition, the team sought to identify biomarkers of mortality in hospitalized patients.

Dr. Goshua and colleagues studied 68 adults hospitalized for suspected COVID-19 – 48 in the ICU and 20 outside the ICU. Patients in the ICU received mechanical ventilation, while the non-ICU patients required supplemental oxygen (≤3 L/min per nasal cannula).

There were more men than women (69% vs. 31%) in the ICU population but not in the non-ICU population (40% vs. 60%). There were no statistically significant differences in age or comorbid conditions between the ICU and non-ICU patients.
 

Results and interpretation

Consistent with augmentation of the coagulation cascade – and as expected – D-dimer and thrombin-antithrombin levels were high in both the ICU and non-ICU populations, but levels were significantly higher (P < .001) among the ICU patients.

Endogenous anticoagulants (antithrombin and proteins C and S) and fibrinolytic enzymes (alpha 2-antiplasmin) were preserved, verifying that CAC is distinct from disseminated intravascular coagulation. Classic fibrinolysis did not occur, as PAI-1 was high in ICU and non-ICU patients, and lysis-30 was normal in nearly all ICU patients (96%).

Von Willebrand factor antigen and activity levels and factor VIII levels were markedly elevated in non-ICU and ICU patients, but they were significantly higher (P < .001) in the ICU cohort. This supports the hypothesis that endothelial cell damage and platelet activation play major roles in CAC.

Similarly, soluble P-selectin, which is shed from endothelial cells and platelets, was dramatically elevated in ICU patients in comparison with controls and non-ICU patients (P < .001 for both comparisons).

Levels of soluble thrombomodulin, which is released from endothelial cells, were not significantly different in ICU patients and controls. However, given thrombomodulin’s significant role in the coagulation cascade, Dr. Goshua and colleagues plotted receiver operating curves to see if soluble thrombomodulin levels were predictive of mortality.

The results showed that soluble thrombomodulin correlated with the probability of survival, both overall and in ICU patients. Soluble thrombomodulin levels greater than 3.26 ng/mL were associated with significantly worse survival in all patients (P = .0087) and ICU patients (P = .0309).
 

Influence on therapy

Laboratory perturbations were detected in both ICU and non-ICU patients, and otherwise healthy outpatients have exhibited potentially life-threatening CAC, according to Dr. Goshua.

These findings suggest the prothrombotic state occurs early in the pathogenesis of SARS-CoV-2 infection, is driven by platelet activation and endotheliopathy, and becomes more pronounced with worsening severity of infection.

The results of this study prompted a change in how Yale–New Haven Hospital manages COVID-19 patients. Patients without a clinical contraindication now receive aspirin at 81 mg daily in addition to the anticoagulation regimen typically used for all hospitalized COVID-19 patients.

Investigations regarding other medications that can influence platelet-endothelial cell interactions and modulate endothelial cell damage in CAC – such as dipyridamole, defibrotide, and eculizumab – are planned.
 

Challenges and unanswered questions

Virchow’s triad was described by the eminent German physician, Rudolf Virchow, MD, in the 19th century. It refers to the three broad categories of factors that can predispose patients to thrombosis — circulatory stasis, hypercoagulability, and endothelial injury.

Although all of these elements could be operative in CAC, the current study suggests platelet activation and endothelial cell injury in CAC may be of primary importance.

Because of the limited ability to test critically ill patients and concerns regarding exposure of additional hospital personnel to COVID-19 patients, the current report lacked clarity about the relationship of the detected laboratory abnormalities to confirmed thrombotic events.

It is unknown whether endothelial cells in different organs are damaged uniformly. It is also unclear if the laboratory abnormalities identified in this analysis can be used to monitor response to therapy, to guide follow-up management of discharged patients with CAC, or to identify infected outpatients who should receive prophylactic anticoagulation.

The mechanism by which SARS-CoV-2 injures endothelial cells is not explained by these data. Neutrophil defensins and other prothrombotic peptides or markers of inflammation could play key roles in pathogenesis, assessment of disease severity, or monitoring for therapeutic efficacy.

Today, we have more sophisticated diagnostic tools than Dr. Virchow had. We also have the ability to record and rapidly disseminate information globally. Still, with regard to the COVID-19 pandemic, clinicians face many of the same challenges that confronted Dr. Virchow in his era.

The analysis conducted by Dr. Goshua and colleagues goes a long way toward elucidating some of the mechanisms and therapeutic targets to meet these challenges.

Dr. Goshua disclosed no conflicts of interest.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

SOURCE: Goshua G et al. EHA Congress. Abstract LB2605.

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